Abstract Purpose Cytokines are released as part of an inflammatory reaction in response to strength exercise to initiate muscle repair and morphological adaptations. Whether hormonal fluctuations induced by the menstrual cycle or oral contraceptives affect inflammatory responses to strength exercise remains unknown. Therefore, we aimed to compare the response of cytokines after acute strength exercise in naturally menstruating women and oral contraceptive users. Methods Naturally menstruating women (MC, n = 13, 24 ± 4 years, weekly strength training: 4.3 ± 1.7 h) and women using a monophasic combined pill (> 9 months) (OC, n = 8, 22 ± 3 years, weekly strength training: 4.5 ± 1.9 h) were recruited. A one-repetition-maximum (1RM) test and strength exercise in the squat (4 × 10 repetitions, 70%1RM) was performed in the early follicular phase or pill free interval. Concentrations of oestradiol, IL-1β, IL-1ra, IL-6, IL-8, and IL-10 were assessed before (pre), directly after (post) and 24 h after (post₂₄) strength exercise. Results IL-1ra increased from pre to post (+ 51.1 ± 59.4%, p = 0.189) and statistically decreased from post to post₂₄ (– 20.5 ± 13.5%, p = 0.011) only in OC. Additionally, IL-1β statistically decreased from post to post₂₄ (– 39.6 ± 23.0%, p = 0.044) only in OC. There was an interaction effect for IL-1β (p = 0.038) and concentrations were statistically decreased at post₂₄ in OC compared to MC (p = 0.05). IL-8 increased across both groups from post to post₂₄ (+ 66.6 ± 96.3%, p = 0.004). Conclusion We showed a differential regulation of IL-1β and IL-1ra between OC users in the pill-free interval and naturally cycling women 24 h after strength exercise, while there was no effect on other cytokines. Whether this is associated with previously shown compromised morphological adaptations remains to be investigated.