Mohammed Kudus gave the Hammers the lead, before Spurs fought back via goals from Dejan Kulusevski, Yves Bissouma and Heung-min Son, having also forced an own goal from Hammers keeper Alphonse Areola. Kudus would also see red in the second-half after clashing with Spurs pair Micky van de Ven and Pape Sarr.
On the Kudus dismissal, Lopetegui later said: "I can't see the action on the TV but we have to accept and this is the kind of action we have to avoid. We need the right behaviour to compete and fight until the end with 11 players.
"For sure we are disappointed. We came here with big expectations, knowing the difficulties we would have against Tottenham, who are one of the best teams in the Premier League. In the same way, trying to believe in us.
"We did well in a lot of moments until the first minutes in the second half and the second goal.
"We have to keep our principles until the end to be able to be strong as a team in the bad moments. That is one thing we have to learn.
"Bad things happen but you have to compete until the end with the right mentality".