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Wearable stretch sensors have potential applications across many fields including medicine and sports, but the accuracy of the data produced by the sensors over repeated uses is largely unknown due to a paucity of high-cycle fatigue (HCF) studies on both the materials comprising the sensors and the signal produced by the sensors. To overcome these limitations, using human physiologically-based parameters, stretch sensors were subjected to quasi-static testing and HCF with simultaneous capture of the signal. The strain produced by the sensor was then compared to the strain produced by testing instrument, and the results suggest that the output from the stretch sensors is strongly correlated with output from the testing instrument under quasi-static conditions; however, this correlation deteriorates under fatigue conditions. Such deterioration may be the result of several factors, including a mismatch between the material response to fatiguing and the signal response to fatiguing. From a materials perspective, the shape of the stress-life curve for the polymers comprising the sensors conforms to the Rabinowitz-Beardmore model of polymer fatigue. Based on these results, consideration of the material properties of a stretch sensor are necessary to determine how accurate the output from the sensor will be for a given application.