It was the NRL restart Newcastle weren't hoping for, losing both captain Mitchell Pearce and starting hooker Connor Watson to injury inside 10 minutes.
Pearce copped a head knock and was bleeding from his cheek before Watson hurt his ankle making a tackle shortly after.
Both won't return in the third-round encounter.
LIVE BLOG:Newcastle Knights v Penrith Panthers at Campbelltown Stadium | round 3
It meant debutants Chris Randall and Brodie Jones came off the bench and joined rookie fullback Tex Hoy earlier than anticpated against the Penrith Panthers at Campbelltown Stadium.
Hoy helped save one try over the line and centre Bradman Best another but Penrith eventually captialised to open their account via Viliame Kikau account midway through the half.
An eight-point try followed shortly after when Knights winger Edrick Lee made contact with Kurt Capewell's head.
Newcastle forward Jacob Saifiti barged over on the stroke of half-time and Hoy added the extras from in front.
The Panthers lead 14-6 at the break.
EARLIER KNIGHTS NEWS:
