To investigate potential mechanisms associated with the increased prevalence of temporomandibular joint disorders among women, the study objective was to determine sex-dependent and region-dependent differences in fixed charge density (FCD) using an electrical conductivity method. Seventeen temporomandibular joint (TMJ) discs were harvested from nine males (77±4 years) and eight females (86±4 years). Specimens were prepared from the anterior band, posterior band, intermediate zone, medial disc and lateral disc. FCD was determined using an electrical conductivity method, assessing differences among disc regions and between sexes. Statistical modeling showed significant effects for Donor Sex (p=0.002), with cross-region FCD for male discs 0.051±0.018 mEq/g wet tissue and 0.043±0,020 mEq/g wet tissue for female discs. FCD was significantly higher for male discs compared to female discs in the posterior band, with FCD 0.063±0.015 mEq/g wet tissue for male discs and 0.032±0.020 mEq/g wet tissue for female discs (p=0.050). These results indicate FCD contributes approximately 20% towards TMJ disc compressive modulus, through osmotic swelling pressure regulation. Additionally, FCD regulates critical extracellular ionic/osmotic and nutrient environments. Sexual dimorphisms in TMJ disc FCD, and resulting differences in extracellular ionic/osmotic and nutrient environments, could result in altered mechano-electro-chemical environments between males and females and requires further study.