Jayawardene hit a half-century in the fourth match, but also injured his knee.
Abu Dhabi: Injured middle-order batsman Mahela Jayawardene has been ruled out of Sri Lanka's last two matches against Pakistan and returned home, team manager Anura Tennekoon said on Tuesday.
The 34-year-old batsman hit a half-century in his team's 26-run defeat in the fourth match in Sharjah on Sunday, but played in some discomfort after injuring his knee.
Tennekoon said Jayawardene has returned home to regain fitness ahead of next month's tour of South Africa.
"After Sunday's game, Mahela's injury got worse so he has returned home," Tennekoon told AFP. "
Chamara Silva was brought in as cover."
Pakistan have an unassailable 3-1 lead in the one-day series, with the fifth and final match to be played on Wednesday.
The 31-year old Silva has played 11 Tests and 74 one-day internationals for Sri Lanka.
Tennekoon said captain Tillakaratne Dilshan was okay after hurting his left thumb and if it does not get worse, he will be available to play in the Twenty20 match between the two teams on Friday.
"Dilshan is okay and will play in the fifth one-day," said the team manager.
Pakistan won the first match by eight wickets before Sri Lanka levelled the series with a 25-run victory in the second. Pakistan won the third match by 21 runs.
Pakistan captain Misbah-ul Haq said his team will put everything into the final match.
"We have to go all-out and win the last game as well and finish the series on a high," said Misbah, whose team will go fifth in the ICC one-day rankings if they win the series 4-1.