Ball Python opening mouth when holding it?

Wat makes you think its not respiratory? It does sound like it to me, that is the usual reason for a snake to keep it's mouth open. Could do with knowing what temperature you run her at and what you are keeping her in. Have you tried putting her head up to her ear to see if you can hear any wheezing, is there any "bubbling" of the nose or mouth?

Your ball python iis sensing the heat coming off your face and will try to get near it. When you hold your ball python do you let it climb freely or do you move when it gets in an uncomfortable spot if so it's trying to find a stable spot

It's really simple. You're obviously pissing the snake off, and it's trying to eat your face.

Well, how long ago did you feed said python? She could be re-adjusting her jaw after feeding. pretty much every snake does that. It may be pure coincidence that she is moving towards your face. If her mouth is gaping and looks to be red (NOT PINK) o the inside, and/or if you notice any gurgling sounds or bubbly mucous coming from the snake, then it needs to be checked for a respiratory infection, as a gaping mouth is the first sign of that. Also, does she often lift her head up a lot instead of keeping it on the ground, almost as if she's looking at the sky or ceiling for prolonged amounts of time? If so, that's called "stargazing" and it's a sure sign that she's having breathing trouble and needs to be checked by a vet. I would say you're probably not pissing off the snake unless she's hissing at you or she strikes at you/bites you. If behavior continues, call a local vet that sees snakes and other reptiles on a regular basis (if you're int the northern Virginia area, SEVS - Stahl's Exotic Veterinary Services - is a good one), and ask your questions, and they may advise you to make an appointment and have your snake checked... Also, mine used to hiss at the TV when it was on, but she's since gotten used to it...do you have a TV on in the area that you handle her? Also, how old is your snake? If she's a baby, she could potentially be frightened...but normally their reaction is to get very tense and hide/flee...she could just be "exploring". Is you python captive bred or wild caught? If it's wild caught and you haven't had it very long, it may not be tame, and could be reacting to you in an odd way. Best of luck dealing with you snake, hope she's ok, and good choice of pet! Cheers!