Hampshire’s police and crime commissioner blamed social media influencers for the incident, claiming they were setting challenges for each other and the wider public.
Donna Jones said children were taken to hospital after taking high doses of the popular painkiller at the weekend.
Now the city council has launched an investigation into the latest social media craze.
A joint statement issued on behalf of the council and other organisations including South Central Ambulance Service and University Hospital Southampton said: “We are aware of the incident in question and are continuing to work across the appropriate agencies as part of ongoing investigations and to ensure those involved are fully supported.
“We are unable to comment any further.”
It comes after shocking footage of rowdy youths charging through Westquay shopping centre and other parts of the city centre was posted on TikTok last month.
As many as 150 people are said to have taken part in the “meet and greet”, which has been likened to a riot.
READ MORE: TikTok videos show rowdy teenagers charging through Westquay
Earlier this month flash mob looting in London’s Oxford Street was said to have been prompted by social media videos and screenshots encouraging youngsters to loot J D Sports and other stores.
Details of the paracetamol incident emerged on the BBC Radio 4 Today programme.
Mrs Jones said: “What’s happened in Southampton is that young people aged 15-17 decided to challenge each other to take a paracetamol overdose to see who could get hospitalised and who could get hospitalised the longest, with the person remaining in hospital for the most hours being the person who won the challenge.
“It’s incredibly worrying, it’s putting young people’s lives in danger.”
She told the Mail Online it was a “TikTok challenge”. The social media platform says it did not host any content related to the incident.
Royston Smith, Tory MP for Southampton Itchen added: “People need to understand, before it’s too late, that social media such as TikTok is more than a source of entertainment, it’s potentially dangerous to our children’s minds and their lives.
“The latest incident in Southampton demonstrates just how dangerous these social media platforms can be.”
READ MORE: Youtuber speaks out after Westquay meet-and-greet goes wrong
TikTok has denied responsibility for the Oxford Street looting, claiming other social media was responsible.
Asked about the paracetamol incident the company said it had not located any content relevant to the challenge.