Valencia managed a spirited draw in France, but the two goals conceded in the first leg meant that it was always an uphill battle to qualify for the quarter-finals.
"We're disappointed to be out of the competition, but we gave everything we had in the second leg," UEFA.com quotes Mathieu as saying.
"We really played to the best of our ability and we were close to going through. Unfortunately, when you concede two goals at home it becomes very difficult.
"The first leg cost us in the end. We weren't focused enough and didn't defend their counter-attacks well enough."
Mathieu has made six appearances for Valencia this season.