Cronulla Sharks have three key forwards out for Sunday's meeting with the second-placed Penrith Panthers.
Regular starters Paul Gallen (knee injury), Wade Graham (hamstring) and Andrew Fifita (knee) are all unavailable.
It means a debut for young back-rower Jack Williams as well as a first appearance of the season for former Cowboys prop Braden Uele and Scott Sorensen.
Uele has only played one NRL game, while he was with North Queensland, while Sorensen has made five appearances across the past two years.
The trio played strongly in Newtown's 58-4 mauling of Newcastle in the Intrust Super Premiership on Saturday in Cessnock.
Winger Sione Katoa, who broke his jaw on his NRL bow in round one, also impressed for Newtown at the weekend but he will stay in reserve grade this week.
Back-rower Luke Lewis, who picked up a corked knee in last weekend's loss to the Dragons, will be given as long as possible to recover before Flanagan makes a decision on his involvement against Penrith.
Flanagan will have to find a new skipper for the Panthers as both co-captains in Gallen and Graham are in the casualty ward.
The Sharks coach, meanwhile, admits the club have been missing James Maloney since the five-eighth swapped clubs with Matt Moylan and joined Penrith.
While Cronulla are 13th, with just two wins from six games, the Panthers have seen Maloney set up four tries and score one of his own in the past three weeks as they've made their best start in 19 years.
Speaking of Maloney, Flanagan said: "We're definitely missing his football ability. His ability to read a game and put his back-rowers into good positions to carry the football. His vision, his temperament. Nothing seems to faze him or worry him."
Cronulla are 51/50 to beat the Panthers, who are 5/6. The Sharks are 93/100 with a six-point start.
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