England international Tuilagi has struggled with injuries over the past couple of seasons but he managed to get back to full fitness to feature in the final warm-up fixture against the Ospreys.
The 26-year-old centre strained the meniscus in his left knee in Leicester's 27-23 loss against Bath in their first game of the Aviva Premiership season on Sunday.
Tigers head coach Matt O'Connor has now confirmed the Samoa-born star is facing 12 weeks on the sidelines when he has the operation although the injury is not as bad as first feared.
"This is not the knee that Manu injured last season and this is not a major injury in the context of what kept him out for the first half of this year," he said. "Manu has worked really hard with the medical and conditioning teams to come back from long-term injury and was starting to find his feet again on the pitch, but he's just been very unlucky with this one.
"It was an innocuous bump, a freak incident in the game. On closer inspection there is some damage to the meniscus which needs to be addressed. We look forward to having him back at the end of his recovery period."
Tuilagi is now a serious doubt to feature for the Red Rose in the Autumn internationals, with the first contest against Argentina on November 11.