Can I use multiple mailing lists for one email - one to send and the other two to exclude?

Hi there, I'll be sending an EDM to a group of people in the mailing list (csv file). I was asked to exclude two groups of people who are on two separate CSV files. I know how to upload a list so that I can send the EDM to the people on the list but not sure if I can upload three lists and use one for sending and the other two for excluding. Could someone tell me if I can do this? Otherwise, how do I go about this?