My guess is heart attack. He wasn't exactly a slim figure in recent years. Just watch Starsky & Hutch (He played Manetti).
Reservoir Dogs is nice, but I'll always remember Chris Penn most for his performance in Best of the Best, a movie which featured Eric Roberts, another actor living in a sibling's shadow.
i was going to mention best of the best, where he played travis brickley and used the best pickup line i have heard in a movie--
standing outside the women's restroom in a bar--
"hey, you going number one or number two?"
brickley had lots of class.
chris penn is perhaps less famous than sean but i always enjoyed his performances more. never really cared for sean penn.
btw, reports say he weighed close to 270 pounds. anyway, i would think drug overdose is probably considered 'natural causes' in california?