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Defending premiers Penrith have fought hard to secure a 16-10 NRL win over South Sydney but will hope Nathan Cleary's ankle complaint is not serious.

Defending NRL premiers Penrith have allayed concerns about their early season form by defeating South Sydney 16-10 but face a nervous wait for the results of scans on Nathan Cleary's ankle.

The NRL is also investigating claims star Souths fullback Latrell Mitchell was the victim of racial abuse from a spectator as he left the field for half-time at BlueBet Stadium on Thursday night.

"The NRL was immediately informed of the alleged matter, and the club will work with the NRL to investigate," the Panthers said in a statement.

Penrith felt the absence of departed premiership-winners Viliame Kikau and Api Koroisau in their shock opening-round loss to Brisbane but Cleary's boot re-energised their attack and had them back in the winner's circle.

The scoreline did not do justice to a contest which was dominated by the Panthers, before being almost snatched at the death by the fast-finishing Rabbitohs and their chief architect Mitchell.

After coming off second-best in a tackle with Alex Johnston, Cleary opted not to kick for goal when an Izack Tago try extended the Panthers' lead to 8-0 before the break. He managed to play the game out, albeit with ankle strapping and a limp.

He is set for scans during Penrith's bye week and could be joined by teammates; coach Cleary hinted other members of the side came into half-time sore but declined to provide further details.

"(Nathan) didn't seem too worried at half-time after they looked at it. There were a couple of guys injured at halftime," Cleary said.

"We'll have to assess it tomorrow."

The ankle complaint came at the end of a strong 40 minutes for the Panthers, who could have been up by more than 10-0 at half-time had recruit Luke Garner not been denied two tries and Isaah Yeo one.

Cleary terrorised the back three with his high kicks, especially inexperienced winger Izaac Thompson, and got the result he was after in the third minute.

The ball bounced in the red zone and travelled through hands to Stephen Crichton, who scored on the right edge.

The Rabbitohs did well to rebuff the Penrith juggernaut as it rolled forward and looked set to go into the break trailing by only four points.

That was until Jarome Luai broke free down the left side and managed to kick for the speedy Tago even as he was tackled.

South Sydney were slow to come out of half-time and, having been battered through the middle the whole first half, appeared too tired to mount a comeback when Panthers winger Brian To'o sailed over on the right side in the 52nd minute.

But after talking the talk during the week with claims the premiers were showing "cracks in their windscreen", Mitchell walked the walk with the ball in the second half.

He came up with an offload to help the prolific Alex Johnston to score his first-ever try at BlueBet Stadium, and then paved the way for Isaiah Tass to score when he broke the line in the final two minutes.

Souths scrambled to level the scores in the dying exchanges but had left their run too late.

"To use a boxing analogy, we tried to fight off the ropes," said Souths coach Jason Demetriou.

"I don't think we stepped into the fight enough. We've got to be better."

The Panthers have now won 10 of their last 11 games against the Rabbitohs.