Playing his first competitive game since January after recovering from an anterior cruciate ligament tear to his right knee, the centre scored a try in his side's defeat on Sunday.
However, it has now been confirmed that Tuilagi picked up another injury during the encounter, which is expected to rule him out until December.
A Leicester statement confirmed: "Leicester Tigers centre Manu Tuilagi faces a spell on the sidelines after suffering a knee strain in Sunday's Aviva Premiership opener.
"Tuilagi recovered from long-term injury in time to start the final warm-up fixture against the Ospreys and then opening game of the campaign against Bath, but he strained the meniscus in his left knee during the match. He will have surgery and recovery time is estimated at 12 weeks."
Tuilagi has not played for England since March 2016 and has made just three starts in the last four years due to a string of serious injuries.