Little is known concerning the contributions of oxidative phosphorylation (OxPhos), anaerobic glycolytic rate (AnGly), maximum creatine kinase (CK) activity, and metabolic economy (ME) on fatigue resistance. The purpose of this study was to model fatigue using muscle tissue metabolic measures during a maximal short-duration isometric contraction. Muscle metabolic function was measured with [31P]-magnetic resonance spectroscopy (MRS) in 54 premenopausal women (age: 33.8 ± 6.3 y) while they performed 100% isometric plantar flexions. Multiple regression analysis revealed that all metabolic variables were independent predictors of fatigue resistance after adjusting for maximum isometric force generated (R2 = 0.56). ME accounted for the largest portion (36%) of overall shared variance. OxPhos accounted for the most shared variance of the three energy systems. These results support previous findings that OxPhos, AnGly, CK, and ME all contribute to fatigue resistance over a short duration. Additionally, the continued activity of CK at the end of 90 s of maximal exercise lends support to the concept of a CK shuttle facilitating energy transfer within the mitochondria. © 2007 NRC Canada.