After meeting with consultants this week, Leeds United confirmed their centre-forward has ruptured his plantar fascia, the part of his foot he suffered his previous injury in.
Since mid-September Bamford has also had ankle, hamstring and quad muscle injuries, limiting him to only two starts since.
Leeds have said the expected recovery time is a minimum of six weeks, and he is just over a week into that. The Whites' final game of the season is in eight weeks.
It makes it unlikely Bamford will be able to make the squad for England's four post-season Nations League. After that there are only two more games - also in the Nations League - before Gareth Southgate names his World Cup squad.
"He has played with a plantar fascia injury for the last 12 months and despite treatment and a prolonged period of rehabilitation, the injury has progressed from a partial tear to a full rupture," revealed Leeds's head of medicine and performance Rob Price.
Goalkeeper Illan Meslier is expected to be fit to face Southampton on Saturday after severe bruising to his upper thigh and lower torso in a challenge which saw Raul Jimenez sent off at Molineux.
Kalvin Phillips, Liam Cooper, Diego Llorente, Raphinha and Mateusz Klich are all expected to be fit to face the Saints.