Standard equipment for the CLS includes two-stage front airbags, sidebags in the front and windowbags. Sidebags in the rear doors are available as an option.

In the event of a side-on collision, the sidebags and windowbags on the impact side are able to deploy simultaneously after a pre-defined delay. The windowbags unfold like an inflatable curtain between the A and C pillars, so potentially offering additional head protection for passengers in front and rear. The front airbags are activated in two stages, depending on the severity of a possible frontal collision.

In addition, the restraint system is fitted with satellite sensors in the radiator area that can operate in conjunction with the crash sensor in the centre console to determine the strength of a frontal collision more precisely and more quickly.

Automatic child seat recognition, which is available as an option, prevents the front airbag from deploying if a Mercedes-Benz child seat with transponder is fitted on the front passenger seat. Belt tensioner and sidebag remain active in order to protect the young seat occupant.

All the seats are fitted with a 3-point seat belt and head restraint. The front seats feature crash-responsive NECK-PRO head restraints. During a rear-end collision these can move forwards and up by sensor control, so potentially considerably reducing the whipping motion of the head.

Belt tensioners on the front and rear seats pull the belts taut against the body in the event of a frontal or rear-end collision of a specific severity. The belt force limiters (adaptive in the front) increase occupant safety in a frontal collision, since they can ensure that the tension is released in a controlled manner once a set limit has been reached.

An additional roll-over sensor in the airbag control unit triggers all of the belt tensioners and both windowbags in certain roll-over situations.