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Soccer is a team sport characterized by repeated high-intensity sprints followed by brief periods of recovery. Repeated sprints with (RCOD) and without (RSA) change-of-direction has therefore been recognized as an important fitness component. The purpose of the present study was to examine the differences in physiological responses between RSA and RCOD, and the relationship with Yo-Yo intermittent recovery test (YYIR1), as an estimate of aerobic capacity, in female soccer players. Thirteen female soccer players (age: 20.8 ± 2.6 years) participated. All players performed an RSA and RCOD test, as well as a YYIR1 test. Total time, fatigue (dec%), lactate ([La]b), rating of perceived exertion (RPE) and heart rate were recorded for each sprint test along with total distance covered in the YYIR1. RSA induced significant higher dec% (8.0 ± 3.0% vs. 5.0 ± 2.4%, p = 0.008, ES = 0.89), [La]b (13.5 ± 3.1mml/L vs. 9.9 ± 3.0mml/L, p = <0.001, ES = 2,25) and RPE (8 vs. 7, p = 0.003, ES = 1.0) compared to RCOD. The heart rate recovery was significantly faster for RCOD compared to RSA (173 ± 11 bpm vs. 178 ± 8 bpm, p = 0.02, ES = 0.89). No significant correlation could be found between aerobic capacity and RSA and RCOD variables. RSA was a more physiological taxing test compared to RCOD when the protocols were matched for sprint duration. This information can help athletes and coaches that are involved in women’s soccer to design and adapt training strategies in the future.