Abstract: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with estimates indicating that ~50% of the world’s population will acquire a head injury at some point in their lifetime (Maas et al., 2017). Mild TBIs account for ~80% of all reported cases, with up to 43% of all TBI patients reporting symptoms beyond 2 weeks post-injury. As of 2016, only 7% of preclinical TBI experiments included both male and female sexes, and fewer studies analyzed the data using sex as a biological variable (Spani et al., 2018). Since 2016, there has been a bigger push for TBI research to include both sexes, due to reports of sex disparities in symptom presentation, recovery, and vulnerability to other neurological disorders; emphasizing how little we know about the pathophysiology of TBI in females. In this Perspective, we discuss some preclinical and clinical sex differences, challenges addressing female inclusion in preclinical TBI research, and potential solutions towards finding a balance between female sex inclusion and sex as an independent biological variable; forging a path towards improving scientific rigor, reproducibility and inclusivity for evaluating pathophysiological sex-differences after TBI.