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Background: Early morning off (EMO) refers to off-states in the morning in people diagnosed with Parkinson's disease (PwPD). This study determined the clinical manifestations of EMO and the association with nocturnal sleep problems and quality of life (QOL) in Chinese PwPD. Methods: In this multicenter, observational, cross-sectional study, data concerning the clinical manifestations of EMO were collected from PwPD in Shanghai by questionnaire. The stepwise logistic regression was performed to analyze the potential risk factors, as well as whether EMO was an independent risk factor for functional dependency in daily life. The mediation analyses were conducted to evaluate whether nocturnal sleep problems might mediate the association between EMO and the QOL. Results: Among the 454 subjects evaluated, EMO occurred in 39.43% of PwPD across all disease stages. The prevalence of EMO increased as the Hoehn and Yahr stage increased and was observed in 35.60% of patients in stages 1–2.5 and 48.85% of patients in stages 3–5. EMO was associated with non-motor symptoms (NMSs). The predominant NMSs associated with EMO were nocturnal sleep problems (98.90%), mood/cognition impairment (93.90%), decreased attention/memory (91.60%), gastrointestinal symptoms (91.60%), and urinary urgency (90.50%). The QOL of PwPD with EMO was significantly reduced (P < 0.001). Moreover, nocturnal sleep problems might partially mediate this relationship (indirect effect: β = 13.458, 95% boot CI: 6.436, 22.042). Conclusion: PwPD have EMO throughout all stages of the disease. Patients with EMO have severe motor symptoms and NMSs. EMO decreases the QOL in PwPD and this relationship is partially mediated by nocturnal sleep problems. In light of these findings, it is suggested that recognition and appropriate treatment of EMO and nocturnal sleep problems could improve the management of PwPD. [ABSTRACT FROM AUTHOR]