The aim of this study was to determine how unilateral pain, induced in two knee extensor muscles, affects muscle coordination during a bilateral pedaling task. Fifteen participants performed a 4-min pedaling task at 130 W in two conditions (Baseline and Pain). Pain was induced by injection of hypertonic saline into the vastus medialis (VM) and vastus lateralis (VL) muscles of one leg. Force applied throughout the pedaling cycle was measured using an instrumented pedal and used to calculate pedal power. Surface electromyography (EMG) was recorded bilaterally from eight muscles to assess changes in muscle activation strategies. Compared to Baseline, during the Pain condition, EMG amplitude of muscles of the painful leg (VL and VM-the painful muscles, and RF-another quadriceps muscle with no pain) was lower during the extension phase [(mean ± SD): VL: -22.5 ± 18.9%; P < 0.001; VM: -28.8 ± 19.9%; P < 0.001, RF: -20.2 ± 13.9%; P < 0.001]. Consistent with this, pedal power applied by the painful leg was also lower during the extension phase (-16.8 ± 14.2 W, P = 0.001) during Pain compared to Baseline. This decrease was compensated for by an 11.3 ± 8.1 W increase in pedal power applied by the non-painful leg during its extension phase (P = 0.04). These results support pain adaptation theories, which suggest that when there is a clear opportunity to compensate, motor adaptations to pain occur to decrease load within the painful tissue. Although the pedaling task offered numerous possibilities for compensation, only between-leg compensations were systematically observed. This finding is discussed in relation to the mechanical and neural constraints of the pedaling task.