Robbie Keane will miss the next four to six weeks for the LA Galaxy after having surgery on his right knee on Thursday.
The striker joined up with Republic of Ireland for a pair of friendlies last week but did not train. He told his national team he did not know how the injury occurred.
Keane posted a photo of his leg on Instagram and the Galaxy later confirmed his prognosis.
"Operation done speedy recovery hopefully back soon stronger," the 35-year-old wrote.
Keane has scored twice for the Galaxy in their first thee MLS games this season.
He joins the team's list of injured players, which already includes Steven Gerrard, Giovani dos Santos, Ashley Cole, Jelle Van Damme and Dan Kennedy.
Gerrard will not face Vancouver on Saturday after missing the past two weeks of training with a calf injury, while Dos Santos (leg) and Kennedy (groin) are also unlikely to recover in time.
Keane also faces a race to get healthy in time for the European Championship, where Ireland begin on June 13.
Ireland coach Martin O'Neill has already said he will likely find some role for Keane at Euro 2016 even if he does not make the squad.
Keane wasn't the only Ireland player to suffer a knee injury last week, as goalkeeper Rob Elliot will miss several months after damaging his anterior cruciate ligament.