Road traffic collisions are a major issue for public health. Depression is characterized by mental, emotional and executive dysfunction, which may have an impact on driving behaviour. Patients with depression (N = 39) and healthy controls (N = 30) were asked to complete questionnaires and to drive on a driving simulator in different scenarios. Driving simulator data included speed, safety distance from the preceding vehicle and lateral position. Demographic and medical information, insomnia (Athens Insomnia Scale, AIS), sleepiness (Epworth Sleepiness Scale, ESS), fatigue (Fatigue Severity Scale, FSS), symptoms of sleep apnoea (StopBang Questionnaire) and driving (Driver Stress Inventory, DSI and Driver Behaviour Questionnaire, DBQ) were assessed. Gender and age influenced almost all variables. The group of patients with depression did not differ from controls regarding driving behaviour as assessed through questionnaires; on the driving simulator, patients kept a longer safety distance. Subjective fatigue was positively associated with aggression, dislike of driving, hazard monitoring and violations as assessed by questionnaires. ESS and AIS scores were positively associated with keeping a longer safety distance and with Lateral Position Standard Deviation (LPSD), denoting lower ability to keep a stable position. It seems that, although certain symptoms of depression (insomnia, fatigue and somnolence) may affect driving performance, patients drive more carefully eliminating, thus, their impact.