It is unknown if fatigue measures like the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) appropriately describe fatigue in Hispanics, or if acculturation plays a role in fatigue. This study compared fatigue in community samples of Hispanics and Anglos. The MFSI-SF and pertinent questionnaires were administered to adults in San Diego County via telephone survey. Some differences in fatigue were observed in initial comparisons between Hispanics and Anglos, including when acculturation was considered. When age and education were controlled, Hispanics reported less general fatigue than Anglos, regardless of acculturation status, p ≤ .01. Exploratory factor analyses indicate that the MFSI-SF general fatigue subscale was problematic for Hispanics. Implications, limitations, and future directions are discussed.