Mack Hansen has been ruled out of Ireland's meeting with New Zealand in Chicago with Jimmy O’Brien and Tom Farrell added to the travelling party.
Bundee Aki and Robbie Henshaw remain doubts for the game with the All Blacks, but will travel with the squad on Tuesday.
However, Munster pair Edwin Edogdo and Brian Gleeson, who were due to head to America as cover, drop out of Andy Farrell’s squad due to injury.
Hansen suffered an aggravation of a foot injury in Connacht’s agonising 28-27 loss to the Bulls on Saturday.
While he will not travel to Chicago, Connacht head coach Stuart Lancaster said Hansen is "optimistic" about the recovery.
While he wouldn't be drawn on a return date, Lancaster confirmed Hansen is walking without a boot and could yet feature at some stage in the Quilter Nations Series games against Japan (8 November), Australia (15 November) and South Africa (22 November).
"He’s obviously disappointed to miss out on the travel to Chicago, but he’s in good spirits," he said.
"It’s very early days. From a scheduling point of view, we haven’t got any games for a while (after Saturday’s interpro with Munster, Connacht are not in action again until 29 November when they host the Sharks).
"We need to make sure he is right. If that means he can contribute to Ireland, then he will obviously.
"He will stay with us for the time being and if he gets fit enough in the next couple of weeks, he will put his best foot forward for Ireland."
Aki also made his seasonal debut for the province in the loss and although he continues to nurse a hip injury, he will be part of the Irish squad that heads Stateside.
Henshaw, meanwhile, was replaced after 56 minutes of Leinster’s loss to Munster at Croke Park but will also be on the plane despite a groin issue.
It’s a big opportunity for Munster centre Farrell who remains uncapped despite his first international call coming back in the 2019 Six Nations, while O’Brien is included a couple of months after making his 100th appearance for Leinster.
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The pair will remain in the squad for the remaining November internationals.
Concussion has hampered Edogdo’s Chicago plans with Gleeson missing out due to an elbow injury having started so brightly against Leinster, scoring his side’s first try in the 31-14 win on Jones’ Road.
The Irish squad will depart Tuesday for an extended training camp before their meeting with the All Blacks at Soldier Field on Saturday, 1 November.
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