The automatic climate control system allows the driver and front passenger to adapt the climate in their respective seats to suit their individual requirements – independently of each other. The system keeps the temperature at the desired level automatically, even in strong sunlight. To this end, sensors register the temperature inside and outside the S-Class, controlling the heating, cooling and fan for each temperature zone individually, according to requirements. Would you like the air to be cool, but are too sensitive to draughts? Then the "Diffuse" automatic mode is just the thing for you. The "Medium" mode, on the other hand, is stronger; and the "Focus" mode distributes the air in a focused manner in the vehicle interior. The system also includes an activated charcoal filter.

The temperature of the footwells can be adjusted independently of that of the rest of the vehicle interior; it can be warmer or cooler. Separate rear air conditioning is available as an option for the two rear zones. A control unit on the rear face of the centre console allows the rear passengers to set their preferred climate individually. As well as offering an automatic mode, the unit features manual controls with which the air temperature and distribution can be set separately for the left and right sides.