A multi-instrument sealing mechanism is provided. The multi-instrument sealing mechanism includes a cannula seal, a cannula cap, an instrument guide (504, 506), an instrument seal (520), and door mechanisms (510) in the instrument guide. The cannula seal can include a cross-slit seal. The cannula cap can capture the cannula seal between the instrument guide and the cannula. A door mechanism and instrument seal can be housed in the instrument guide.