Something said to someone meaning that they should not be ashamed of anything or that they shouldn't be sad. It means that they should not stare at the ground in despair but rather pick their head up and stand tall.
Jim: John, why are you so sad?
John: I fucked Sally Parker and she's pregnant.
Jim: Sally Parker?! She's hot as fuck. Head up.
Jim: We just lost the state championship. I am so sad.
John: You guys are a great team and came a long way. Head up.