This study aimed to evaluate whether the trajectory of the body's Centre of Mass (CoM) is a sensitive and responsive measure of functional compensations in individuals with knee osteoarthritis (OA) performing the Five Times Sit-to-Stand test (5STS). This prospective study included 21 individuals with OA and 21 age- and gender-matched controls. Motion analysis data was collected while participants performed the 5STS, one month prior and one year after total knee arthroplasty (TKA). Pain was evaluated using a visual analogue scale. Repeated measures ANOVAs were used to evaluate (1) differences in the area under the curve (AUC) of CoM trajectories, and (2) the effect of number of sit-to-stand cycles on the AUC. Preoperatively, individuals with OA displayed a larger contralateral shift (p = 0.009) and forward displacement of the CoM (p < 0.004) than controls. Postoperatively, CoM trajectories of OA individuals were not statistically different from controls. However, upon comparison of specific cycles, OA individuals displayed a larger forward displacement during the final cycle. Pain was significantly reduced postoperatively (p = 0.001). The CoM trajectory appears to be a sensitive and responsive measure of functional compensations. The increased contralateral shift of the CoM represents a strategy to reduce pain by unloading the affected knee. Postoperatively, when pain was substantially reduced, OA individuals were comparable to controls. The increased forward CoM displacement characterises a strategy to reduce muscular effort by reducing the required knee extension moment. Postoperatively, OA individuals were comparable to controls in all cycles but the last, possibly suggesting residual muscle weakness.