Numerous occupant protection systems can significantly reduce the risk of injury during an accident. Examples include the NECK-PRO head restraint, a standard feature on the front seats: when the sensor detects an impact from the rear, it thrusts the head restraint forwards in a matter of a few milliseconds to reduce the gap between it and the occupant's head.

As standard, the C-Class is equipped with seat-belt tensioners on the front and outer rear seats, as well as various airbags, including two-stage driver and front-passenger airbags and windowbags whose protection zone covers virtually the entire area of the side windows. Particular development effort was invested in the sensors that trigger the front airbags. The necessary restraint system performance is adjusted to the driver and front passenger based on an occupant classification function. With that the C-Class establishes another trend in safety technology: individualization of restraint systems. The sidebags and windowbags also feature a newly developed control technology: pressure sensors, which see use for the first time in a Mercedes-Benz in the C-Class. If the door deforms in a side-on collision, the increase in air pressure between the body panels and the interior of the door is registered by the pressure sensors, which assist the control unit in deploying the sidebags and windowbags.

Furthermore, other road users are also protected by means of the body's smooth surfaces and its excellent programmed yielding characteristics.