Arsenal entertain the Hammers at Emirates Stadium just six days after the sides played out a goalless Premier League draw in Stratford.
The Gunners have just passed the halfway point in a month in which they will play nine matches, and Wenger confessed fatigue is an issue in his squad.
"Some players are a little bit on the edge," said the Arsenal boss.
"I think as well that we have so many quality players who did not start on Saturday, so you cannot say that you prefer to play a player who has played three games in six days to a guy who is at the same level and is completely fresh.
"The players who will start are basically all international players, so that's why I think [squad rotation] makes sense. You have to show the trust and the confidence that we have in the players."
Wenger has used the Carabao Cup and Europa League to hand opportunities to the likes of Matt Macey, Joe Willock and Eddie Nketiah, that latter scoring a double to see them past Norwich City after extra time in the previous round.
The trio are among a number of Arsenal youth products to sign new contracts in recent months and the Frenchman hopes to continue aiding their development.
"It's a very exciting bunch of young players," Wenger said. "I made the decision a few months ago to try and keep them at the club because I believe they all have futures at the club.
"I am convinced as well, but it is very important for Arsenal to continue giving chances to young players we educate here.
"For example, on Saturday, we had four players who have been developed in our academy - Alex Iwobi, Jack Wilshere, Hector Bellerin and Ainsley [Maitland-Niles].
"That shows you that our level you have not many teams who can show up with that. That's a positive sign. We have some good young players coming through as well, behind them."