The aims of this study were to examine sex differences in college students while they performed cardiopulmonary resuscitation (CPR) on a manikin for 20 min in (a) objective and subjective effort indicators and (b) to analyse the influence of potential confounders (age, BMI and cardiorespiratory fitness) on these sex differences. Sixty-three participants were recruited. Participants performed 20 min of CPR on a manikin. During the CPR trial, percentages of maximal heart rate levels were higher in women than in men (P<0.05) and perceived exertion increased significantly in both sexes over time (P=0.05); furthermore, at the last two time points analysed, women scored higher than men (P<0.05). However, these sex differences disappeared when controlling for age, BMI and cardiorespiratory fitness. In conclusion, indicators of exertion during CPR are higher in women than in men, but these sex differences are because of BMI and differences in physical fitness conditions.