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Background: This pilot trial explores the feasibility of measuring muscle contractile properties in patients with cancer, effects of exercise during chemotherapy on muscle contractile properties and the association between changes in contractile muscle properties and perceived fatigue. Method: Patients who received (neo)adjuvant chemotherapy for breast or colon cancer were randomized to a 9‐12 week exercise intervention or a waitlist‐control group. At baseline and follow‐up, we measured knee extensor strength using maximal voluntary contraction (MVC), contractile muscle properties of the quadriceps muscle using electrical stimulation, and perceived fatigue using the Multidimensional Fatigue Inventory. Feasibility was assessed by the proportion of patients who successfully completed measurements of contractile muscle properties. Exercise effects on muscle contractile properties were explored using linear regression analyses. Between‐group differences >10% were considered potentially relevant. Pearson correlation (rp) of changes in contractile muscle properties and changes in perceived fatigue was calculated. Results: Twenty two of 30 patients completed baseline and follow‐up assessments. Measurements of contractile properties were feasible except for muscle fatigability. We found a potentially relevant between‐group difference in the rate of force development favoring the intervention group (1192 N/s, 95% CI = −335; 2739). Change in rate of force development was negatively correlated with change in perceived general (rp = −0.54, P =.04) and physical (rp = −0.59, P =.02) fatigue. Conclusion: Chemotherapy induces a decrease in the rate of force development, which may reflect a larger loss in type II muscle fibers. This may be attenuated with (resistance) exercise. The increase in the rate of force development was related to a decrease in perceived fatigue. [ABSTRACT FROM AUTHOR]