Background: Fatigue is a common and disabling non-motor symptom (NMS) of Parkinson’s disease (PD); however, it has been poorly understood in patients with progressive supranuclear palsy (PSP). We investigated the association between fatigue, clinical features, and other NMS in patients with probable PSP.Methods: In 72 probable PSP patients, fatigue was investigated using the PD fatigue scale (PFS). Further, all patients were evaluated using the PSP rating scale (PSPRS), Beck Depression Inventory (BDI), Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), PD Sleep Scale (PDSS), NMS scale (NMSS), PD Questionnaire-39 summary index (PDQ-39 SI), and Scale for Outcomes in PD-Autonomic (SCOPA-AUT). Results: The prevalence of fatigue was 38.9% (28/72) in patients with PSP. Logistic regression analysis showed that depression (BDI) was the factor associated with fatigue. We divided the patients into primary (fatigue without depression, n =16), secondary (fatigue with depression, n = 12), and non-fatigue groups. There were no differences in age, sex, disease duration, and PSPRS, PDSS, MMSE, and FAB scores among the three groups. The primary fatigue group had higher scores in PDQ-39 SI compared to the non-fatigue group. The secondary fatigue group showed higher scores in NMSS, PDQ-39 SI, and SCOPA-AUT compared to the non-fatigue group. PFS was positively correlated with NMSS and PDQ-39 SI and SCOPA-AUT.Conclusions: Fatigue is common in patients with PSP and is associated with the NMS and the quality of life in these patients. The present study provides meaningful insight into fatigue in patients with PSP.