Obstructive sleep apnea (OSA) is characterized by collapse of the upper airways during sleep. The contribution of alterations in effort perception is not understood. This study investigated the response of inspiratory and quadriceps muscles to repetitive loading on effort perception in OSA patients, pre and post continuous positive airway pressure (CPAP) treatment, and in healthy individuals. Twenty-one OSA patients and 40 healthy participants completed protocols for repetitive inspiratory and leg muscle loading combined with intermittent rating of perceived exertion (RPE 14—somewhat hard/hard) to assess effort sensitivity. Electromyography, inspiratory pressure and isometric force were measured. OSA patients reported higher fatiguability of respiratory and leg muscles than controls. OSA patients revealed lower effort sensitivity in the leg muscles compared with controls, while repetitive loading led to a decline in force production. In the respiratory system, OSA patients revealed similar effort sensitivity at baseline compared with controls, but a large reduction in effort sensitivity after loading. Baseline effort sensitivity was correlated with apnea-hypopnea index (AHI). After CPAP treatment, OSA patients revealed a decreased baseline effort sensitivity with a missing loading response. Effort sensitivity was differentially affected in the respiratory and leg systems with outcomes of CPAP treatment suggesting a full reversibility. Outcomes suggest that reversible adaptive response of effort perception in the respiratory system might contribute to the severity of OSA.