Effective treatments for multiple sclerosis (MS)-associated central fatigue have not been established. Surface functional electrical stimulation (FES), which can challenge the peripheral neuromuscular system without overloading the central nervous system, is a relatively safe therapeutic strategy. We investigated the effect of 8 weeks of surface FES training on the levels of general, central, and peripheral fatigue in MS patients. Seven of nine individuals with MS (average age: 42.86 +/- 13.47 years) completed 8 weeks of quadriceps muscle surface FES training. Maximal voluntary contraction, voluntary activation level, twitch force, General Fatigue Index (FI), Central Fatigue Index (CFI), Peripheral Fatigue Index, and Modified Fatigue Impact Scale (MFIS) scores were determined before and after training. The results showed that FI (p = 0.01), CFI (p = 0.02), and MFIS (p = 0.02) scores improved significantly after training. Improvements in central fatigue contributed significantly to improvements in general fatigue (p < 0.01). The results of the current study showed that central fatigue was a primary limitation in patients with MS during voluntary exercise and that 8 weeks of surface FES training for individuals with MS led to significantly reduced fatigue, particularly central fatigue.