Herpes is a sexually-transmitted disease that has made two appearances on the series. It first referenced in the Season Two episode, "Chickenpox", and was later seen in the Season Sixteen episode, "I Should Have Never Gone Ziplining".
Frida has the disease in "Chickenpox". Stan Marsh finds out that chickenpox is actually a form of herpes, and the boys get revenge on their parents for deliberately causing them contract the virus. They hire Frida to use their parents' various personal hygiene products, most notably their toothbrushes.
Kenny had contracted the disease in the episode "I Should Have Never Gone Ziplining". Cartman frequently made fun of him for having the disease, though Kenny claimed that is was only a cold sore. Kenny later died, but not from the herpes.