BACKGROUND: Fatigue of air force pilots has become an increasing concern due to changes in mission characteristics. In the current study we investigated fatigue, emotions, and cognitive performance in a simulated 11-h mission in the 39 Gripen fighter aircraft. METHODS: A total of 12 subjects were evaluated in a high-fidelity dynamic flight simulator for 12 consecutive hours. Perceived fatigue was measured by the Samn-Perelli Fatigue Index (SPFI). Emotions were assessed with the Circumplex Affect Space. Cognitive performance was assessed by five cognitive tasks. RESULTS: Significant increase in self-reported fatigue, general decrease in two positive emotional states, as well increase of one negative emotional state occurred after approximately 7 h into the mission. Self-reported fatigue negatively correlated with enthusiasm and cheerfulness (r' = -0.75; -0.49, respectively) and positively correlated with boredom and gloominess (r' = -0.61; r' = -0.30, respectively). Response time in the low-order task negatively correlated with enthusiasm, cheerfulness and calmness (r' = -0.44; r' = -0.41; r' = -0.37, respectively) and positively correlated with boredom and anxiousness (r' = 0.37; r' = 0.28, respectively). Mission duration had an adverse impact on emotions in these environmental conditions, particularly after 7 h. DISCUSSION: These results contribute to the understanding of fatigue development in general and of emotion-cognition relationships. These findings emphasize that both emotional states and the type of cognitive tasks to be performed should be considered for planning long-duration missions in single-piloted fighter aircrafts as to increase the probability of missions' success.