Bargnani, Toronto's leading scorer on the season, left the game with a strained left calf and the Sacramento Kings took full advantage.
Led by a season-high 29 points from Tyreke Evans, they snapped a seven-game losing streak in Toronto by defeating the Raptors 98-91 on Wednesday.
It was the first win in Toronto for the Kings since Feb. 22, 2004.
Leandro Barbosa came off the bench to score a season-best 24 points for the Raptors. Bargnani finished with 10 points and 10 rebounds.
Bargnani said he would have a magnetic resonance imaging done on Thursday but feels the injury was similar to one had last season.
"He doesn't remember doing it," Raptors head coach Dwane Casey said. "It's similar to last year. It's a lot of fatigue. You see a lot of it around the league right now with fatigue, pulls and that type of thing."
The Raptors (4-7) led 56-55 when Bargnani left the game and it was tied 63-63 at the end of the third quarter.
But the Kings (4-7) took command in the fourth quarter and led by 10 points with 42 seconds to play.
Evans scored 14 points in the fourth quarter when he was 9 for 9 from the free-throw line. He was 14 for 14 on the game in free throws and also had seven rebounds.
DeMarcus Cousins added 21 points on 6-for-11 shooting from the field and 9 for 11 from the free-throw line and grabbed 19 rebounds for the Kings.
Isaiah Thomas had 12 points in the fourth quarter and finished with 20 points for the game and had six assists. Jimmer Fredette chipped in with 10 points for Sacramento.
"It was a big confidence builder for us, because in the other road games we were getting blown out," Thomas said. "The coach always preaches to us to stay in the game for the first three quarters and we can try to win it in the fourth."
It was the second loss in a row and fourth in five games for the Raptors. Jose Calderon had 13 points to go with 10 assists for Toronto.
DeMar DeRozan also scored 13 points on 5-for-9 shooting while Linas Kleiza scored 10 points in his first game since undergoing right knee surgery last February. Amir Johnson had nine points and six rebounds before fouling out with 37.4 seconds to play.
"I feel good, it's fun to be back," Kleiza said. "Of course the game didn't end the way we wanted but for me personally, after a year off, it feels good to be back. I've got a lot of people to thank and this is just the beginning, but it is a good first step."
Added Calderon: "We're happy to have him back, he's going to help us a lot that's for sure."
Kleiza may be relied on even more in the short term, with Bargnani's status unknown.
"Well, (Bargnani) is our best player," Calderon said. "It's tough to see him go out and after they let us know that he wasn't coming out again, it was tough."
Sacramento pulled ahead in the fourth quarter 80-73 with seven minutes to play when Thomas hit a three-pointer.
Cousins hit a pair of free throws with 1:28 to play and made a dunk 16 seconds later to put Sacramento ahead 86-77.
The lead reached 10 points but the Raptors came back and narrowed it to five points on Barbosa's jumper with 24 seconds left.
"The game got away from us a little bit but we were able to regroup and make the right plays," Kings head coach Keith Smart said. "I thought our bench guys came in and gave us the lift we needed to have on back-to-back games."
The Raptors were playing their third game in as many nights while Sacramento was playing for the second consecutive night. Both teams lost on Tuesday, Toronto at Washington and Sacramento at Philadelphia.
The concentrated 66-game schedule is a result of shortened season due prolonged labour dispute between owners and players.
"Again, the guys I can't fault their effort,” Casey said. "The guys were really fighting, scratching and clawing. There's no quit in our guys and that's what I like, too. Defensively we have gotten better, some way we've got to get some execution offensively."
Notes: Attendance at Air Canada Centre was 14,423. ....Raptors shooting guard DeRozan entered Wednesday's game mired in a 12-for-46 (26 per cent) funk from the field for a total of 31 points in the previous four games. ... Toronto guard Jerryd Bayless (sprained left ankle) missed his eighth game in a row ... Kleiza who had knee surgery performed last Feb. 1, entered the game late in the first quarter and played 14:28 on the game. ... Forward Chuck Hayes (dislocated left shoulder) was out for Sacramento. ... The Raptors are home to Indiana on Friday, their seventh game in nine days.