"Our luck is not getting any better, is it?" said Leicester director of rugby Richard Cockerill, who has already lost fellow centres Antony Allen and Matthew Tait until January and December respectively.
"Manu's was just one of those things in a collision. It's a straightforward break and he will be out for six weeks."
Tuilagi was one of the standout players in England's disappointing World Cup campaign, offering a constant attacking threat with his powerful running and direct approach.
The Samoan-born former England Under 20s star only made his senior international debut in the summer but was already being billed as a certain starter for next year's RBS 6 Nations.
Tuilagi will now face a real battle to be ensure he retains his England place as he is unlikely to be back in domestic action until the second-week in December at the earliest.
The news is yet another blow for Leicester who have already lost England scrum-half Ben Youngs to a knee injury.
Youngs returned from England duty with a reoccurrence of the damage he first sustained during the summer and now faces second spell out in quick succession.
Tuilagi and Youngs will be joined on the physio table by Allen, who damaged a thumb in a freak DIY accident, and Tait, who aggravated a groin injury.
"Ant (Allen) was doing some DIY at home and cut his thumb," added Cockerill.
"He has had surgery and it will take three months to heal."