Police were called to the collision southbound on Newgate Lane, near to the entrance of Tudor Lodge at 10.20am on November 17.
The collision involved a yellow and red coloured skip lorry, a blue Nissan Micra, a grey Kia Sorento and a white BMW 2 series.
The 57-year-old female driver of the Kia was taken to Queen Alexandra Hospital, Cosham, with minor injuries and was later discharged.
The 72-year-old male driver of the Nissan was also taken to Queen Alexandra Hospital. His condition is described as serious.
PC Michael Nol said: “This collision happened on a busy section of road, not long after the morning rush hour, so we know that there would have been a lot of people around who may have seen something.
“We would like to speak to anyone who witnessed the collision or saw any of the vehicles prior to the incident.”
Anyone with information is asked to contact PC Nol on 101, quoting 44160434134, or Crimestoppers anonymously on 0800 555 111.