Cow, is Chicken's 7-year-old cow sister, with a weight stated as 600 pounds. She is usually viewed (at least by Chicken) as exceedingly infantile and stupid, and is quickly prone to emotional outbursts, but she occasionally displays uncanny talents. Though she looks up to her older brother, Chicken, thinking that he is cool and usually lovingly addresses him as "Big Brother", it has been shown many times that she would not hesitate to use blackmail to get Chicken to do what she wants, proving that she has all of the mischief and wit of a younger sister used to getting her way in all things, due to her status as the baby of the family.

Chicken, (voiced by Charlie Adler), is one of the two main characters in Cow and Chicken Cow's 11 year old chicken brother. He can be mean to his younger sister, and even to the rest of the family. He has a powerful ego, but in spite of this, has a powerful conscience, usually only displayed when Cow is in danger, as well as being more intelligent (and sane) than most characters, and his selfish actions can actually come to others help.