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. Rosa E, Gronkvist M, Kolegard R, Dahlstrom N, Knez I, Ljung R, Willander J. Fatigue, emotion, and cognitive performance in simulated long-duration, single-piloted flight missions. Aerosp Med Hum Perform. 2021; 92(9):710719.