Leon Barnett fired Wigan into an early lead, but Thorgan Hazard brought the visitors level before half-time after an error from goalkeeper Lee Nicholls, and a fine late 20-yard strike from Bernard Malanda gave the Belgians a 2-1 win at the DW Stadium.
Asked for his verdict, Boyce said: "Very disappointed. I thought we were controlling the game especially in the first half.
"The first (Zulte-Waregem) goal was a bit soft from our point of view and we couldn't quite get a foothold back in the game.
"The second goal was a hammer blow for us. We thought we'd done enough to get a result here.
"Now we have to go to our last game and get a victory, and hopefully the other team does us a favour."
Wigan are relying on their conquerors of Thursday night slipping up at home in two weeks' time against Group D winners Rubin Kazan, who have nothing to play for.
Wigan will need the three points from their own trip to face Slovenians Maribor to stand any hope.
"We create so many chances but we can't put them away at the moment," Boyce said on BT Sport.
"The boys did well in the first half but in the second half we just ran out of gas.
"It's a cruel game sometimes. Fair play to the lad (Malanda), he scored a good goal, but from our point of view we should have been home and dry."
Boyce defended Nicholls, who got hands to Hazard's shot but could only palm the ball into the back of the net for the equaliser. With Scott Carson injured, the 21-year-old has seen plenty of recent action.
"Lee's come in and does really well. We're not going to point the finger at anyone. He's only a young boy," Boyce said.
"He's pulled some fantastic saves off this season and he's got to pick his head up now."
Boyce still believes FA Cup winners Wigan can advance from the group in their first season in Europe.
"We're Wigan: we like doing things the hard way," he said.
"We'll go away from home and know we need three points.
"It's going to be a tough task but we're confident we can go there and get a result."