Toffees boss Rafael Benitez confirmed that attacking midfielder James is one of the players he will be without in Sunday's (AEST) clash with the Saints at Goodison Park because of COVID-19 protocols.
The former Liverpool manager said: "We have some players who are in isolation and we have to manage that.
"We have to be very careful, and some players have to be at home. James is one of them.
"I will not name too many players because I think it is better not to do it."
Strike duo Richarlison and Dominic Calvert-Lewin will be available to take on Ralph Hasenhuttl's side.
Richarlison returned to training on Wednesday after winning a gold medal for Brazil at the Olympic Games in Tokyo, while Calvert-Lewin has recovered from a toe injury.