Chelsea boss Thomas Tuchel made eight changes for the game as Kepa, Cesar Azpilicueta, Malang Sarr, Callum Hudson-Odoi, Ross Barkley, Saul Niguez, Timo Werner and Lukaku all started, Werner having shaken off a knock.
The Blues have injury problems in midfield as Mateo Kovacic (coronavirus), Jorginho (back) and N'Golo Kante (knock) are all out.
Full back Ben Chilwell is also out with a knee injury whilst Trevoh Chalobah has been battling a hamstring issue.
Edouard Mendy, Thiago Silva, Ruben Loftus-Cheek and Antonio Rudiger were among those given the night off.
Chelsea went ahead in just the second minute when Timo Werner converted Ross Barkley's corner from close range following a flick on by Zenit's Sardar Azmoun.
The Blues had chances to add to their tally but looked vulnerable at the back and Zenit levelled in the 38th minute when Claudinho glanced a header past Kepa after a mistake from Cesar Azpilicueta allowed Douglas Santos to send in a cross.
The Russians then went ahead just three minutes later as Barkley gave the ball away to Claudinho and Zenit played in Azmoun who rounded Kepa before firing his side in front.
Chelsea equalised in the 62nd minute when a neat move led the returning Romelu Lukaku with a tap in but only a fantastic save from Kepa then kept out an Azmoun header in the 71st minute
The Blues fought back to net what looked set to prove the game's winning goal in the 85th minute as Christian Pulisic played in Werner who shifted inside before firing home a clinical finish past 'keeper Mikhail Kerzhakov.
Yet Zenit provided one final sting in the tail as Sarr's headed clearance fell straight to Magomed Ozdoev who rifled home a terrific finish from the edge of the box.
Lukaku came off in the 75th minute to be replaced by Kai Havertz as one of four substitutions made by Tuchel.
Mendy, Thiago Silva, Loftus-Cheek and Rudiger were all unused substitutes.
The draw meant Chelsea finished only second in Group H behind Juventus who recorded a 1-0 win at home to Malmo.
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Thank you Laura Collins