The Hammers will meet the Premier League leaders on Sunday.
Lopetegui said, "To be afraid? No, afraid no. We have big respect for all the teams, but we have the same respect for Southampton, for Liverpool and all of them.
"We are talking about the best team in the Premier League. Top players, very good coach, they are now in the height but we have to believe in us, in our strength and in our possibility."
He added, "We are talking about the best team in the Premier League now by far. This is enough reason to be ready. Now we have to rest and to be ready for the next challenge.
"It is time to take advantage of the players that we are going to need. It is the moment to highlight the worth of the team with capital letters because we need this.
"We have a lot of problems. All the midfielders out, also we only have two centre-backs, but it happens and we have to be ready. In football, no fear."