Purpose: Examine neuromechanical alterations due to isolated and/or combined knee pain and effusion in functional movements. Methods: A 4X3 randomised controlled laboratory study with repeated measures was used. Nineteen, healthy volunteers (age: 22.4 ± 2.4 years) underwent four different treatments (control, effusion, pain, and pain/effusion) with a week wash out period. Ten near-infrared cameras with 43 reflective markers, 12 surface EMG electrodes, and two ground-embedded force platforms were used to record neuromechanical changes during functional movements (walking and drop landing). To induce pain, 5% sodium chloride (1 ml) was injected into the infrapatellar fat pad. To induce effusion, 0.9% sodium chloride (50 ml) was injected into the knee joint capsule. To induce pain/effusion, both injections were employed. No injection was used for the control. Subjects performed walking and a single leg drop landing in three time intervals: precondition (prior to injection), condition (immediate post injection), and postcondition (30 min post injection). To quantify pain perception, the visual analogue scale was measured every two minutes. Results: Under pain/effusion treatment, subjects walked slowly with a shorter stride length. Joint moments of plantarflexion, knee extension, knee abduction, and hip abduction were reduced. Subjects also showed a decrease at 20% and 80% of stance phase, and an increase in 50% in vertical ground reaction force (VGRF). Under the same treatment, subjects landed with a less peak VGRF with increased time to peak VGRF, alterations of joint angles (ankle dorsiflexion, knee extension, and hip adduction), and moments (knee extension, knee abduction, and hip abduction). Conclusions: Joint pain and effusion cause neuromechanical alterations in the lower extremity during functional movements. These compensatory strategies may alter joint loading, potentially resulting in acceleration of the joint degenerative process. We also recommend use of crutches following injury to avoid modifications of movement strategies.