The Ecuador striker opened the scoring in his side’s 2-2 first-leg draw with Romanians Astra Giurgiu but was carried off before half-time.
And West Ham manager Slaven Bilic admitted Valencia’s injury “doesn’t look good”.
“I am worried, to be fair,” he said. “It looks serious but we won’t know for sure until he has a scan.”
Bilic also lost Joey O’Brien to a first-half injury, although the Irishman walked off unaided, and saw another player sent off as James Collins was booked twice inside five second-half minutes.
Collins became the third West Ham player dismissed already this season, and in his absence West Ham blew a 2-0 lead ahead of next week’s return leg in Romania, Angelo Ogbonna’s own goal capping a disappointing second half.
Bilic said: “It was a very frustrating evening because we played well until the moment we had a player sent off. We were dominating the game.
“We had chances to score the third goal. (The first booking) was a professional foul from Collins and I can’t blame him. The second yellow was harsh.
“After that, until they scored a great goal, they didn’t create but they started to hurt us. We had some counter-attacks and chances. They scored one great goal and an own goal, but it was a different game after they scored the first one.
“We definitely played well in the first hour, but the game lasts 90 minutes and we had to react better to going down to 10 men. The problem was also that we could not change a lot because we had already done two substitutions so we had to wait.
“At 2-2 it’s a bad result for us and we’re not happy. Add the injuries to Joey and Enner and the frustration is bigger.”
Of his own sending-off he said: “It looks serious but we won’t know for sure until he has a scan.”