SAM is able to function in 4 unique modes of operation.

Mode 0: Unpressurized, sealed
Mode 1: Unpressurized, flow-through
Mode 2: Pressurized, flow-through
Mode 3: Pressurized, sealed

In Mode 0 the vessel is not pressurized by the lung and pump and the blower is disabled. This is used when the lowest possible leak rate is desired and monitoring the interior, non-circulated, unfiltered air is desired as with human CO2 generation or plant CO2 sequestration studies are conducted. Mode 0 offers the lowest leak rate as there is a minimal pressure differential between the inside of the SAM vessel and the outside, ambient atmosphere, resulting in the least quantity of molecules transferred. The temperature difference from inside to outside will invoke a minor differential, but this remains minimal when compared to Mode 2 and 3.

In Mode 1 the vessel is not pressurized by the lung and pump, rather, the blower moves a continuous air stream through SAM to maintain a constant flow of fresh air. This is used for teams that do not desire to maintain the SAM structure in a pressurized state, nor manage the air quality monitor and levels. Valves at all three pressure doors will be open, assuring fresh air is circulating for the duration of the mission.

In Mode 2 the vessel is pressurized and the blower moves a continuous air stream through SAM to maintain a constant flow of fresh air. As the blower is powered by a variable frequency drive (VFD), the volume of air introduced to SAM is ample to both maintain a lifted lung and thereby pressurized state, while also compensating for the intentional loss of air at critical, open ports (e.g. sleeping quarters). This is used for teams that desire a pressurized state, but do not wish to manage a CO2 scrubber.

In Mode 3 the vessel is pressurized and hermetically sealed, meaning significant quantity of air is escaping SAM and the blower is activated only if the lung touches down and the pressure drops to a predesignated minimum (the lung will rise and fall each day with temperature swings while maintaining a continuous, higher pressure over outside ambient due to the mass of the membrane even if the feet of the steel lung pan touch down). Activation of the blower will introduce fresh air, filtered air and represent an ISRU source. The amount will be tabulated and accounted for in the mission data.

When the Test Module functioned as a sealed facility for Biospherian Linda Leigh, it remained inflated (pressurized) for the duration of three weeks with the likely potential to continue for some time more. It is the intent of the SAM crew to prepare a pressure vessel capable of something similar, but given the complexity of a greatly expanded crew quarters it will take some time to determine the potential.