The purpose of the current study was to determine if, and to what extent, sex differences in performance fatigability after a sustained, bilateral leg extension, anchored to a moderate rating of perceived exertion (RPE), could be attributed to muscle size, muscular strength, or pain pressure threshold (PPT) in young, healthy adults. Thirty adults (men: n = 15, women: n = 15) volunteered to complete a sustained leg extension task anchored to RPE = 5 (10-point OMNI scale) as well as pretest and posttest maximal voluntary isometric contraction (MVIC) trials. The fatigue-induced decline in MVIC force was defined as performance fatigability. We used muscle cross-sectional area (mCSA) to quantify muscle size and a dolorimeter to assess PPT. The sustained task induced fatigue such that both men and women exhibited significant ( p < 0.05) decreases in MVIC force from pretest to posttest ( M = 113.3, SD =24.2 kg vs. M = 98.3, SD = 23.1 kg and M = 73.1, SD =14.5 kg vs. M = 64.1, SD = 16.2 kg, respectively), with no significant sex differences in performance fatigability (grand M = 12.6, SD =10.6%). Men, however, exhibited significantly ( p < 0.05) longer time to task failure (TTF) than women ( M = 166.1, SD =83.0 seconds vs. M = 94.6, SD =41.7) as well as greater PPT ( M = 5.9, SD = 2.2 kg vs. M = 3.4, SD =1.1 kg). The only significant predictor of performance fatigability was PPT. In conclusion, differences in PPT, at least in part, mediate variations in TTF during self-paced exercise anchored to a specific RPE and resulting in performance fatigability.