In the E-Class, a wealth of safety systems work in step to help prevent accidents. However, should the worst come to the worst, occupant safety measures come into play, providing protection for both the occupants and other road users. Occupant protection comes in the form of a high-strength safety passenger cell, adaptive front airbags which are deployed in several stages in line with the severity of the impact, and sidebags in front, windowbags and a kneebag on the driver's side.

Then there are the NECK-PRO crash-responsive head restraints for the driver and front passenger: in the event of a rear-end collision above a certain severity, pre-loaded springs push the head restraints by around 56 millimetres forwards and 23 millimetres upwards at lightning speed to support the heads of the front occupants at an earlier stage. This can reduce the risk of whiplash injuries considerably.

The active bonnet is a safety feature for the protection for other road users and helps reduce the risk of injury to pedestrians and bicyclists. If a collision occurs the rear section of the active bonnet rises up by five centimetres using spring force. This produces additional deformation space to absorb the impact and in particular to prevent serious injury.