Michael Maguire's nightmare weekend has gone from bad to worse after NSW State of Origin hopeful Nicho Hynes was a late withdrawal from Cronulla's clash against Melbourne.
AAP understands the Sharks halfback reported calf tightness, less than 24 hours after Nathan Cleary's hamstring injury appeared to strengthen his case for an Origin recall.
Probable Blues centre Tom Trbojevic is set to miss the first two games of the series after injuring his right hamstring in Manly's loss to the Dolphins on Thursday and facing a seven-week rehabilitation period.
The Sharks are yet to confirm the length of their halfback's lay-off, though believe the issue is minor.
Any absence of more than two weeks would cast doubt over Hynes' ability to join the Blues for Origin I camp, which begins in the final week of May.
Cleary limped from the field in Penrith's 16-10 win over Canterbury on Friday night, and went for scans on his right hamstring on Saturday afternoon.
The Panthers were still awaiting the results early on Saturday evening, but the club are preparing to be without their halfback for the coming weeks.
Even the smallest of tears would leave Cleary in doubt for Origin I at Accor Stadium in Sydney on June 5.
Cleary was a certain selection for Maguire at No.7, with Trbojevic expected to line up next to him at right centre.
Those plans now need serious alterations.
Mitch Moses would ordinarily be the frontrunner to replace two-time Clive Churchill medallist Cleary, but the Parramatta playmaker has his own injury woes.
Moses may return from a foot injury against Melbourne next Sunday, but is far from a certainty to play.
If he does not feature in that match, he will have only one game - against South Sydney on May 25 - before Maguire names his first team.
Hynes had been a five-eighth option, but that plan may also need to be reassessed, with Jarome Luai and Matt Burton two possibles for the No.6 jersey.
Trbojevic's injury is also problematic, with the 2021 Wally Lewis Medal winner only likely to make game three at best.
Fellow fullback-turned-centre Latrell Mitchell has reportedly considered making himself unavailable for NSW amid Souths' horror start to the season.
Stephen Crichton could return to the side at centre, while incumbent Bradman Best's chance of holding his spot are firming.
Kotoni Staggs is another option, while Maguire could play Burton or Zac Lomax at centre.
Despite NSW's nightmare 24 hours, Penrith and Blues lock Isaah Yeo remained confident in his side's chances of winning back the Origin Shield.
"At the start of the pre-season, (Maguire) brought in a 36-man squad on the understanding that things like this happen," Yeo said.
"There's been other players since the camp too.
"Thirty-six players were picked for that, because injuries happen, particularly at this time of year.
"I've got all the confidence in the world that the boys will go in and do a wonderful job."