Ed Joyce has been ruled out of Ireland's one-day games against South Africa and Australia later this month.
The Sussex batsman, 37, requires minor knee surgery and has been replaced in the squad by Sean Terry, who made his debut against Afghanistan in July.
Tim Murtagh will join the squad in South Africa after Middlesex's final County Championship game next week.
Ireland face South Africa in Benoni on 25 September before meeting Australia at the same venue two days later.
"It's obviously a blow to lose someone of Ed's calibre but Sean Terry is a batsman of undoubted promise," said Ireland coach John Bracewell.
"Given the likely pitch in Benoni, and the likelihood we will facing two majority pace attacks, the selectors felt that Sean was the logical replacement."
Joyce produced impressive form for Ireland over the summer as he hit two centuries against Afghanistan at Stormont, including a series-saving unbeaten 160.
Murtagh, 35, will delay his departure to South Africa in order to be available for Middlesex's County Championship game against Yorkshire, starting on Tuesday, as they aim for a first title in 23 years.
"This match means a huge amount to both Tim and Middlesex. Having played with the club for 10 years, it would be the culmination of one of his most fiercely held ambitions," said Cricket Ireland's performance director Richard Holdsworth.
Middlesex have agreed to fly Murtagh out to South Africa as soon as the game finishes, in time for him to join the squad ahead of the first game against South Africa.