The Spain international returned to his homeland to attend the birth of his daughter and, due to the current laws, needed to have a quarantine period upon his return to Manchester.
De Gea is due to finish his spell of isolation today (Sunday), with Dean Henderson selected against the Hammers, and two more keepers, Lee Grant and Nathan Bishop on the substitutes' bench.
It is hoped that the 30-year-old will be allowed to return to training on Monday, ahead of the midweek trip to Italy to face AC Milan in the Europa League.
The Reds are then at Leicester City for an Emirates FA Cup quarter-final before an international break.