Assistant coach Gruff Rees suggested that the former Wales U21 captain had dislocated his left knee when he spoke to the press immediately after the game and the Ospreys medical team have now confirmed that the injury is a serious one.
"Tom suffered a significant knee injury and we are carrying out all relevant investigations in order to determine the full extent of the injury and the way forward for Tom in terms of treatment and rehabilitation. A further update will be issued as appropriate," read an Ospreys statement.
The news is yet another bitter blow for Smith after he missed the majority of last season with a groin problem.
Voted Coaches' Player of the Year in the region's most recent RaboDirect PRO12 title winning campaign in 2011/12, Smith had begun this season brightly, skippering the side in pre-season and in the Round 2 draw with Leinster.
The 27-year-old has started all three competitive games this term but he now looks to be facing a lengthy spell on the sidelines while his team-mates aim to build on their current second place in the standings.
There was at least some good news for the region in the form of Ryan Jones' fitness, though, with the veteran back row cum second row all set to feature in Saturday's clash with Connacht in Galway.
Jones led the Ospreys in the opening win at Treviso but missed the trip to Leinster and the victory over Edinburgh with a shoulder injury.
"He will be available this week. I know I intimated as such the week just gone: the physios are quite cautious but there's nothing to really hold him back," said Rees.
"It's just a case of looking at the fatigue of the group. Ryan will hopefully be someone who is desperate to play and will want to make an impact against Connacht."