As the Storm completed their final training session before flying to Sydney for the BlueBet Stadium clash, halfback Hughes was at the doctors after falling ill, with youngster Jonah Pezet running in his place.
Winger Coates started the session but looked downcast as left the training track with a hip issue.
George Jennings, who was named among the reserves, could be in line for a run-on spot.
Losing Kiwi Test No.7 Hughes and Origin ace Coates would be a massive blow as the Storm look to avenge an 18-point defeat a month ago in round 18, and avoid losing to the Panthers twice in a regular season for the first time since 2005.
Penrith superstar Nathan Cleary missed that round 18 match through injury but has since returned to his sparkling best.
Melbourne coach Craig Bellamy was cagey about whether Hughes would be available.
"Jahrome isn't feeling too well so we will just see what happens for the rest of the day and go from there," Bellamy said.
"Xavier has a little bit of a problem with his hip so we will see how he pulls up as well.
"He just wanted to go in and get some extra treatment.
"I can't say he's definitely going to play - we thought he was going to be better than he was out there today so we will see what the medical people say."
With six matches under his belt since making his debut this season in round three, including three starts, Pezet seems the obvious choice to replace Hughes although Bellamy said that utility, 18th man Tyran Wishart, was an option.
Melbourne bounced back from a disappointing loss to Newcastle to thump Parramatta by 30 points last round.
Bellamy said his fourth-placed side would need to repeat that performance to match ladder-leading Penrith.
In their last meeting the Storm raced to a 14-0 lead before the shell-shocked Panthers regrouped and flexed their muscles in a one-sided second half.
"If we don't bring our best, it won't be good enough," the veteran coach said.
'They've been the benchmark for a few years now so it's obviously a big task.
"We need to be consistent for 80 minutes so hopefully we do that tomorrow night."
Exciting fullback Ryan Papenhuyzen is making his return via the Queensland Cup on the Sunshine Coast on Saturday after almost 13 months out with a shattered knee cap.
Bellamy said he didn't want to see anything special from the fan favourite apart from getting through his comeback injury-free.
"We're looking at him playing 50 to 60 minutes and if he gets through that we will reassess where he's at medically, and also footy-wise and physically as well and then we will plan the next week after that.
"I just want to see him get through the minutes strongly and hopefully without any problems with his knee."
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