The aim of this study was to investigate determinants of self-rated health (SRH) perception in Spanish adults. This cross-sectional study including data from 11,342 participants from the Spanish PLENUFAR VI study. SRH status was grouped in two categories (‘good’/‘poor’) and the associations of socio-demographic characteristics, lifestyles, diet adequacy and chronic disease with SRH were assessed. After adjusting for relevant confounders, the risk ratios (RR) and (95% confidence intervals) for poor SRH were 1.05 (1.03–1.07) for each hour of increment of sitting, 1.56 (1.30–1.88) for short (≥5 h vs. 7–8 h) sleep duration, 0.63 (0.55–0.72) for vigorous (vs. light) physical activity, 0.61 (0.50–0.74) for adequate (vs. non-adequate) diet. Activities like jogging [RR for each unit of increment in the METs-h/day = 0.87 (0.82–0.92)], gymnastics [0.87 (0.81–0.93)], biking [0.91 (0.85–0.98)], and track and field [0.94 (0.89–0.98)], were associated with better health perception. Normally weight participants with any chronic disease had lower probability to report poor SRH than overweight/obese participants with any chronic disease. Frequent consumption of bread (>2 servings/day) was associated with a lower adjusted mean of health perception scale, while higher consumption of vegetables and fruit or fish were associated with higher values, concerning good SRH. We can conclude that normal-weight participants even suffering a chronic disease had lower probability to report poor health perception than participants with overweight/obesity and a chronic disease especially for hypertension and diabetes. Activities like jogging, gymnastics, biking, and track and field, and a higher consumption of fruits, vegetables and fish, were associated with better health rated perception.