Andrew Conway and Jordan Larmour have been named in the Ireland team to face Scotland in their World Cup Pool A opener in Yokohama on Sunday.
Conway will start on the right wing with Larmour at full-back after Keith Earls and Rob Kearney were ruled out.
Kearney has been struggling with a calf injury sustained in training and Earls has been suffering with a quad injury.
Connacht's Jack Carty is named as the replacement fly-half with Joey Carbery recovering from an ankle injury.
Munster's Carbery only returned to training this week having hurt his ankle against Italy in August.
Ireland will also be without centre Robbie Henshaw, who is hopeful of returning to face hosts Japan on 28 September.
The Leinster centre picked up his injury in training last Saturday while provincial team-mate Kearney sustained his problem during another session on Monday.
Earls was injured in Ireland's final warm-up game against Wales, although he did take part in training over the past week.
Earlier this week defence coach Andy Farrell revealed that both Earls and Kearney were fit to play, but with just six days between their opening two fixtures Ireland have opted not to risk the experienced duo from the start.
Joey Carbery has been given additional time to regain full fitness
Carty, who impressed in his only start of the warm-up matches against Wales in Cardiff, will deputise for Johnny Sexton in Carbery's absence.
Conway has played seven of his nine starts on the wing, and is another whose impressive form in the warm-up matches warrants his inclusion in the starting XV.
Against England and Wales Conway was deployed at full-back, with Larmour taking his place on the wing, although the Leinster back has also featured regularly at full-back since his Ireland debut in last year's Six Nations.
Ireland coach Joe Schmidt will hope his side can overcome the loss of Kearney, who has won 95 Test caps for Ireland and the British and Irish Lions, and Earls, who boasts 78 appearances for his country, to claim victory in their vital opening fixture.
Jack Conan misses out on a place in the back row as CJ Stander gets the nod as number eight.
Ireland will face Japan, Russia and Samoa in their other Pool A fixtures.
Ireland: Larmour; Conway, Ringrose, Aki, Stockdale; Sexton, Murray; Healy, Best, Furlong; Henderson, James Ryan; O'Mahony, Van der Flier, Stander.
Replacements: Scannell, Kilcoyne, Porter, Beirne, Conan, McGrath, Carty, Farrell.