Driver fatigue has been the cause of traffic accidents. Despite this, the amount of time that drivers spend within cars has been increasing due to complex city life, traffic congestion, and particular occupational requirements. Consequently, fatigue and stress cannot be avoided. In present study, in order to find out the possibility for reducing fatigue while driving due to the supply of oxygen, driver fatigue resulting from the passage of time when different oxygen concentrations are supplied has been examined through subjective evaluations and reaction times using driving simulator for 10 male subjects. The results revealed the subjective fatigue feeling was highest in the low rate (18%) oxygen condition, while in the high rate (30%), it decreased to a certain extent. The feeling of sleepiness also showed the tendency to decrease somewhat in the case of the driving time having passed over 1h in the high-rate conditions. Also, the reaction time for braking after being instructed to suddenly stop following more than 2h of driving was reduced in the high-rate oxygen conditions compared to the low-rate oxygen condition. From the above results, it was shown that while driving a car, if the oxygen rate is lowered, fatigue is felt severely, and that in the case of supplying a high-rate of oxygen, the feeling of fatigue is lowered to some extent and the reaction time is shortened. It was suggested that the driver's fatigue can be reduced according to the supply of oxygen.