The combined effects of chronic ankle instability (CAI) and lower extremity fatigue on measures of neuromuscular control have not been well established. The purpose of this study was to investigate the influence of CAI on the performance of a dynamic postural control task, the Star Excursion Balance Test (SEBT), after fatiguing activities. Thirty subjects with (n = 14) or without (n = 16) unilateral CAI completed anterior, medial, and posterior reaching directions of the SEBT performed before and after a lunging fatigue protocol and an open chain ankle isokinetic fatigue protocol. Pre-post fatigue change scores were calculated for sagittal plane kinematics of the stance leg and the normalized reach distances (%MAXD). Using a regression model, group and kinematic data were used to explain between subject differences in %MAXD. For each reaching direction, a separate analysis was completed for the two fatigue conditions. When reaching anteriorly after the lunge fatigue condition, CAI and the changes in knee and hip flexion predicted approximately 49 % of the variance in %MAXD (R2 = .487; p = .001). When reaching medially under lunge fatigue, CAI predicted approximately 20 % of the variance in %MAXD (R2 = .198; p = .014). Isolated ankle fatigue did not cause significantly different responses between groups. For two of the reaching directions, CAI status significantly influenced the variances in %MAXD under the influence of lunge fatigue. Functional fatigue protocols