Watkins scored to help England to a 3-0 victory over Wales last week but picked up a knock which will leave him out of the clash against Latvia which would see the Three Lions qualify for the World Cup next year if they pick up three points.
England confirmed his absence on Monday morning in what could also be a huge blow for Villa after the break.
“Ollie Watkins has been ruled out of tomorrow's @FIFAWorldCup qualifier against Latvia, having not recovered from the knock sustained against Wales.
“Speedy recovery, Ollie!”
However, good news for England manager Thomas Tuchel is that captain Harry Kane is expected to return, having missed the Wales friendly with an ankle problem.
England’s top scorer has scored 19 goals in 12 games for club and country this season and won’t let up against Latvia if he starts as he aims to lead his country to yet another international tournament.
Tuchel’s side lead Group K with five wins from five and are yet to concede a goal, and a squad of 22 will travel to Riga in the hopes of qualifying early.