Gun winger To'o initially played on after hurting his leg in a tackle from back-up hooker Peter Mamouzelos in the second half of Friday night's game at CommBank Stadium.
The Panthers took To'o off in the final 20 minutes as a precaution but a representative told AAP the club held concerns for the NSW representative, who has been hampered by injury all season.
To'o's premature exit put a damper on the resurgent Panthers' latest triumph, inspired by stand-in captain Dylan Edwards in the absence of the rested Isaah Yeo and Nathan Cleary.
The fullback crossed for two tries, one after a brilliant To'o run and the second as he grabbed an offload from Luke Garner in the second half.
He added a try assist to his stats sheet by supporting Blaize Talagi up the field and then finding Casey McLean.
McLean capped off the big win by beating five defenders down the left wing for a second try in the final five minutes.
Making their seventh-straight loss even worse, the Rabbitohs lost their shining light Keaon Koloamatangi to an ankle issue suffered as he attempted to tackle Garner in the second half.
He was joined on the sidelines by Mamouzelos, who suffered a head knock colliding with Isaiah Papali'i shortly thereafter.
Alex Johnston chased Jack Wighton's grubber kick to cross for his 207th career try in the final 90 seconds and give the Rabbitohs something to smile about.
Johnston is only five four-pointers away from equalling Ken Irvine's record of 212.
The Rabbitohs are now unable to finish the season with a winning record and have their coach Wayne Bennett on his longest losing streak since 2014.
Souths are on track to finish lower on the ladder than any Bennett-coached side in history, a mark currently held by the inaugural Dolphins side that placed 13th in 2023.
The outlook is rosier for four-time reigning premiers Penrith, who now have one hand on a top-eight spot after slumping to last on the ladder after 12 rounds.
They will be hot favourites in their next three games, all against bottom-eight sides, and are guaranteed a winning record to finish the season if they take care of business in all three.