According to societal stereotypes, the female sex and people who are more feminine have been considered to be more empathic than males and people who are more masculine. Therefore, females and feminine individuals are expected to respond more empathically to an infant’s cries. While this hypothesis was tested using self-report scales, it has not been explored thoroughly in terms of prefrontal cortex (PFC) activity, which may be a more objective means of measuring empathy. Specifically, the medial PFC (mPFC) is involved in social cognitive processing and thus a good proxy to measure the level of empathy. This study aims to (1) assess if the empathic response, in terms of medial PFC (mPFC) activity, to infant cries differ between sexes; (2) investigate if the empathic response is moderated by levels of masculinity and femininity. Functional near-infrared spectroscopy (fNIRS) was used to measure nonparent participants’ (18 males, 20 females) mPFC response to infant cries of different pitches (high and low). The Toronto Empathy Questionnaire was used to measure trait empathy and Bem’s Sex Role Inventory was used to measure the level of masculinity and femininity. Results revealed that biological sex had no significant effect on the empathic response towards infant cries of varying pitch. Furthermore, masculinity, not femininity, was correlated with an increase in empathic response in the mPFC to high but not low-pitch infant cries. We reason that this is because of the higher aversiveness and inflicted pain associated with higher-pitched cries, which induces more emotional and physical pain that masculine individuals seek to avoid. Overall, the results suggest that greater masculinity would imply greater mentalizing and processing of empathy-related information.