It depends on your and your player's sense of humour and creativity. My DM has had to deal with a lot of people whose schedule just conflicts with the majority of the players or who just quit due to personal reasons. One of those who quit at the end of a boss battle in a cave was caught in a cave-in and never found. A player who refused to come to a session and whose schedule changed afterward unexpectedly, his character got infinite diarrhea and had to stay at the inn we were at. Another player left after giving some warning and his character joined the palace guard.
If you think that they might come back one day then leave that open and remind your players of their existence. The player whose schedule changed added to the party by allowing his character to get sold as a slave to gain a vital clue. When he comes back, the entire party will go on a side adventure to free him. If that's not your cup of tea, then just think of something that your group would enjoy and that would fit in with the flavour of your quest and their character. It can serve as a punishment or not, but it's really up to you.