Nuno Espirito Santo's side rescued a 2-2 draw, having fallen behind in the second half.
But the biggest concern will be that Steven Bergwijn and Lucas Moura limped out of the match, adding to their growing injury list.
There was, however, a first start for Tanguy Ndombele under new boss Nuno, with the midfielder having asked to leave the club this summer.
Harry Kane, Steven Bergwijn and Lucas Moura were other high-profile starters as Spurs began their group campaign with their toughest test.
The north London club started well and went in front in the 11th minute.
A fine back heel by Ndombele set Moura free and the Brazilian's cross was deflected in by Loic Bade.
Rennes equalised midway through the first half as Flavien Tait curled low into the bottom corner from the edge of the area.
Spurs lost Steven Bergwijn through injury and were under the cosh for the remainder of the first half.
They were then dealt a further blow when Moura also had to come off after struggling with injury.
Nuno's fell behind in the 71st minute as Pierluigi Gollini spilled a low shot from Kamaldeen Sulemana and Gaetan Laborde had the easiest of tap-ins.
Spurs produced an instant response as Matt Doherty's cross was deflected into the path of Emile-Pierre Hojbjerg and the Dane prodded home from close range.
The game finished 2-2, but with such an important Premier League clash with Chelsea on Sunday, Bergwijn and Moura's doubts ahead of the match will be a worry.
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