Sexton damaged a tendon in his left foot at the end of training on Thursday, resulting in his withdrawal from the starting XV for Saturday's RBS 6 Nations clash with Italy at the Stadio Olimpico.
The 27-year-old had only just recovered from the hamstring injury he sustained against England on February 10 and now faces an even longer spell on the sidelines.
"We were told yesterday that Jonny will be out for four six to weeks," Ireland coach Anthony Foley said.
The prognosis means Sexton will almost certainly miss Leinster's Amlin Challenge Cup quarter-final against Wasps on April 5, leaving him with just two RaboDirect PRO12 fixtures to prove his fitness to Lions selectors.
Lions head coach Warren Gatland is scheduled to announce his squad on April 30, so any setback in his recovery could threaten his involvement with the tour to Australia.
The Leinster playmaker has only completed 120 minutes of Test rugby this year, but counting in his favour is his position alongside England's Owen Farrell as one of the two best fly-halves available to Gatland.
"That was a doctor saying four to six weeks, it wouldn't surprise me if Jonny is two to four weeks away," Foley added. "You take into account his powers of recovery from his hamstring tear and how quickly he came back from that, combined with his attitude to rehab, and he could be back sooner.
"Having worked with the lad this season, I imagine when he gets into the thick of the rehab he'll fly through it, although it will be tough mentally at the start."