The experienced fly-half had to endure a long and painful return journey from the two-game mini-tour which saw Warriors lose to Stormers and Bulls.
Weir started against the Bulls at Loftus Versfeld but it will be his last involvement of the campaign.
Glasgow travelled back from Pretoria via Dubai and it wasn’t the most comfortable journey for Weir.
“Duncan Weir broke his thumb/hand,” said Danny Wilson, the Glasgow coach. “He’ll be out for the rest of the season. He’ll be in a cast.
“It was very swollen and he had an ice pack on it for two flights of eight hours. He got it looked at when we came back and it was confirmed it was broken.”
Ross Thompson will start at stand-off for Glasgow in Saturday’s European Challenge Cup quarter-final against Lyon in France, with Domingo Miotti providing cover on the bench.
Weir’s absence is the latest in a series of injuries for the Scotstoun club who are currently without Fraser Brown, Sebastian Canceilliere, Scott Cummings, Rory Darge, Matt Fagerson, Walter Fifita, Thomas Gordon, George Horne, Rufus McLean and Kyle Steyn.
Canceilliere, Cummings, Darge, Fagerson, and Steyn are unlikely to play again this season.
“We all have these times in the year, unfortunately ours has fallen at the business end of the season when you want to go in with the majority of your squad available,” said Wilson. “But them’s the breaks and if our squad’s going to be successful then that’s exactly what it’s got to be - a squad. So we go again.”
The better news is that Brown should be fit to play some part in the season’s climax.
“Fraser Brown has a shoulder injury and we’re hoping it’s only going to a two or three-weeker but we’ll have to wait and see,” added Wilson.
Glasgow are also through to the play-off quarter-finals of the United Rugby Championship where they will face an away tie against opponents yet to be determined on the first weekend of June.