Mystery surrounds how they came into contact with a nerve agent and who could have administered it, as well as what their motive would have been.
Police are treating the attack as attempted murder, and are investigating several sites around the cathedral city – with the ex-spy’s home among the major crime scenes.
What have they been poisoned with?
Sergei Skripal and his daughter have been hit with a nerve agent, which interrupts the messaging between the brain and the body.
Symptoms include confusion, an abnormal heartbeat, wheezing or problems breathing – and they were seen slumped together.
Nerve agents include substances such as VX, which was used to kill Kim Jong Un’s half brother Kim Jong Nam at Kuala Lumpur airport in Malaysia. Another is sarin – a gas which has been used as a chemical weapon.
Meanwhile, soman is an extremely toxic chemical liquid that is clear and colourless – although it goes yellow to brown as it ages and gives off a vapour. It can kill quickly and is classed as a weapon of mass destruction.
There’s also thallium, a heavy metal known as the poisoner’s poison.
Police have not yet confirmed which agent was used, but it has been described as “very rare” agent, which could only have been produced by a few laboratories in the world.
According to The Sun, one of these is the Yasenevo lab in Moscow.
Hamish de Bretton-Gordon, a chemical weapons expert, told Sky News it is not sarin, or VX, and the other options are soman or tabun.
He said: “It could also be a boutique or exotic chemical weapon that was made for this attack.
“They know what it is, and they can treat it. With Porton Down on the doorstep, they couldn’t be in a better place to be treated for this chemical attack.”
How did this happen?
It is not entirely clear how the pair came into contact with the nerve agent.
Mr Skripal and his daughter had visited a few places in the city centre during the day, including a Zizzi restaurant, and then a pub, before they were found slumped on a park bench.
They could have been spiked when they were dining or drinking – or they may have had the agent sprayed at them as they walked between the venues.
Sky’s Home Affairs Correspondent Mark White said: “We are still unclear about how this nerve agent was administered. Was it sprayed in their face? Slipped into their food or drink?
“We simply don’t know and obviously that will form part of the inquiry.”
According to The Times, police are questioning whether Ms Skripal had been given a “gift from friends” which she had with her on Sunday when they succumbed to the agent.
It could also be that Ms Skripal was collateral damage, and that only her father was meant to be attacked.
Who could have poisoned them?
The overarching theory is that the pair have been targeted by Russia, but whether this is a state sponsor or an individual is less clear.
Mr Skripal had been working as a double agent back in the 1990s. It is understood he was part of a spy swap, which makes it less likely the Kremlin would still be interested in him as a targeted assassination.
The Kremlin has insisted they are not involved, and said any link to them is a plot to whip up anti-Russian sentiment.
An alternative is that the Skripals were targeted by someone with a personal grudge.
Of course, it could also be a case of mistaken identity, where the pair were not the intended targets of the attack at all.
Sir Christopher Meyer, the former UK ambassador to the US who is also a Russia expert having previously worked in Moscow, said: “I would be surprised if anybody in the Kremlin would have organised an operation like this and didn’t really care if they were discovered or not.
“I don’t think that is true.
“You wouldn’t use something as rare and as something to get rid of as a nerve gas, a nerve agent, unless you wanted to conceal your traces.”
Was the assassin targeting Yulia?
Police are understood to be investigating whether the agent was delivered to Ms Skripal as a gift from friends.
Alexander Vissiliev, espionage historian, told Sky News: “Every possibility should be investigated properly. From the point of view of an ex-KGB officer, killing someone, in espionage, doesn’t make any sense in most cases.
“It usually brings a lot of unpredictable consequences and usually the damage is already done, so it doesn’t make any sense to kill him.
“It looks like a Mafia thing to me, like it was arranged by a Mafia type clan. I would investigate his business dealings, if he had any, since he moved to Britain and his son and daughter too, if there are any.
“In 1990s in Russia, businessmen used to kill each other in Russia. Then they moved to Europe, and they moved location but the tactics didn’t change.
“It may be connected to business.”
Ms Skripal is also understood to have been a vocal critic of Vladimir Putin on social media.
Why have they been poisoned?
It is thought by some that Mr Skripal may have still been working as a spy, having not retired after he was offered refuge in the UK.
If this is the case, that may have made him a target.
Sir Christopher Meyer told Sky News there are some “strange things” about the Skripal case.
He said: “What did he do after he had asylum here in the UK?
“Did he continue to work against Russia? Because he might have done something, or been with some British intelligence agency, say, which was such that it enraged people in the Kremlin.
“That is a possibility, but we cannot diplomatically do anything until it is clear beyond all doubt that this was an operation undertaken by the Kremlin.”
Sir Christopher also said that if Mr Skripal is viewed by Vladimir Putin as a “traitor” rather than simply an enemy, he may be a target.
He added: “It’s very easy to say Sergei Skripal is one of those guys and so Putin has eliminated (him). But there are things that stop me making that leap.
“One is, if this guy was such a traitor, why – back in 2006… whenever it was – did he only get 13 years in a Russian jail? Because, normally, a traitor is shot. So, that’s strange.
“The second thing is, he was part of a spy swap. I don’t think there’s any history of ever a Russian agent who’s been part of a spy swap, in that case with the Americans, later being wiped out.”
Who benefits from the poisoning?
Alexander Vissiliev suggests one possibility is that Vladimir Putin is being framed by political adversaries.
He told Sky News: “It doesn’t make sense for him to have someone killed but it means a lot to adversaries.
“This is a total political disaster for Russia, and for Putin personally, but for his adversaries it is a different story.
“We could be dealing with hyper patriotic veterans of the secret service who consider him (Putin) too liberal.”
He also told Sky that this could be a business dealing not a political one, and that he would be investigating the business records of not just Mr Skripal, but his daughter.
Sky’s Moscow Correspondent was unable to find any trace of Ms Skripal as working for Pepsico in the city, which is where she lists her employment on social media.
It could be that the spy was targeted to give a warning to anyone else thinking of crossing the Kremlin.
Yuri Felshtinksy, a friend of Alexander Litvinenko, said: “Poisoning is the method of choice for the FSB.
“This has all the hallmarks of a Putin assassination. He is warning anyone in the FSB never to defect, as they’ll be hunted down and killed.”