We examined the association between self-rated health (SRH), a subjective measure of an individual’s health status, and the incidence of metabolic abnormalities, as well as the effect of obesity on this association in metabolically healthy individuals. The cohort study included 85,377 metabolically healthy men and women who were followed annually or biennially for a median of 3.0 years (interquartile range, 1.9–4.1 years). A parametric proportional hazard model was used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SRH and the incidence of metabolic abnormalities. During 258,689.03 person-years, 40,858 participants developed metabolic abnormalities. Poorer SRH was significantly associated with increased risk of developing any metabolic abnormality including hypertriglyceridemia, high homeostasis model assessment of insulin resistance (HOMA-IR), and fatty liver in a dose-dependent manner (p for trend <0.05). The association between SRH and progression to metabolically unhealthy status was much stronger in individuals with obesity than those without, especially in relation to any metabolic abnormality, fatty liver, and high C-reactive protein (all p for interaction by obesity <0.05). The multivariable-adjusted HR (95% CI) for any metabolic abnormality comparing the “poor or very poor” vs. the “very good” self-rated health category was 0.97 (0.90–1.05) among non-obese subjects, whereas the corresponding HR (95% CI) among obese subjects was 1.25 (1.02–1.52). Low SRH, as assessed by a single question, was independently associated with increased risk of progression to metabolically unhealthy status in metabolically healthy individuals, especially metabolically healthy individuals with obesity. SRH may help identify individuals at high risk for progression to metabolically unhealthy status.