Scotland captain Tuipulotu ruled out of Six Nations
Tuipulotu is due to have surgery on the pectoral muscle he damaged in training with Glasgow Warriors last week.
"Sione Tuipulotu will miss the tournament after sustaining a pectoral muscle injury during a training session with Glasgow Warriors last week," a Scottish Rugby statement said on Monday.
"Sione will undergo surgery this week and is expected to return to action before the end of the season."
Rory Darge and Finn Russell will co-captain Scotland in Tuipulotu's absence as they bid to win the Six Nations title for the first time.
The last time they topped the table was the final Five Nations championship in 1999.
Tuipulotu is a leading contender to claim one of the two starting positions at centre for the British and Irish Lions in Australia later this year.
And while the 27-year-old will not be able to feature in the Six Nations, Tuipulotu is expected to return towards the end of the campaign in a boost to Lions head coach Andy Farrell.
Tuipulotu has won 30 caps since his debut in 2021, emerging as a dynamic midfield force while scoring three Scotland tries.
In another blow to Scotland, lock Scott Cummings is also set to miss the Six Nations with a fractured arm suffered during Glasgow's Champions Cup game against Harlequins on Saturday.
Gregor Townsend's Six Nations squad has been reduced to 36 players, but no additional players will be called up at this point.
Scotland kick off their Six Nations campaign against Italy in Edinburgh on February 1.