Abstarct: Introduction: Scoliosis, as one of the most common three-dimensional spinal deformities, by altering postural alignment, can affect postural control and joint position sense. On the other hand, muscle fatigue, by reducing the efficiency of the neuromuscular system, diminishes the ability to maintain postural stability and the accuracy of proprioception; these effects appear to be exacerbated in individuals with scoliosis. The aim of the present study was to compare the center of gravity (COG) sway and knee proprioception in girls over 18 years of age with scoliosis versus healthy individuals, before and after performing a fatiguing exercise protocol. Methods: This study was of a semi-experimental and comparative type, with a pretest-posttest design in two groups. The statistical population consisted of 18 girls with scoliosis and 18 matched healthy individuals (comparison group), who were screened using the Adams test and a scoliometer. Center of gravity sway was measured using a force plate, and knee proprioception (angle reconstruction error) at three angles of 30°, 60°, and 90° was measured using a handheld goniometer, before and after performing a standard fatigue protocol. Data were analyzed using analysis of covariance (ANCOVA) with pretest control at a significance level of 0.05. Methods: Center of pressure (COP) sway was measured using a force plate, and knee proprioception (joint angle repositioning error) was assessed at three angles—30°, 60°, and 90°—using a manual goniometer, both before and after the administration of a standardized fatigue protocol. Data were analyzed using repeated-measures analysis of variance (mixed ANOVA), with time and angle as within-subject factors and group as the between-subject factor, at a significance level of 0.05. Results: Center of pressure sway did not differ significantly between the two groups in either the pretest or the posttest; moreover, at angles of 30° and 60°, the main effects of group and time and their interaction were not significant. Regarding knee proprioception at 90°, the main effects of group and time were not significant; however, their interaction reached statistical significance. Furthermore, no significant correlation was observed between the repositioning error at each angle and the corresponding center of pressure sway, before and after fatigue induction. Conclusion: Fatigue appears to exert a more specific negative effect on knee proprioception in individuals with scoliosis at high-demand joint angles (90°), whereas its effect on center of pressure sway warrants investigation with a larger sample size. These findings underscore the necessity of incorporating targeted proprioceptive training into the rehabilitation programs of these patients.