Introduction: Obesity is associated with reduced quality of life and reduced life satisfaction, but does weight loss make you happier? The objective of this study was to investigate if body mass index (BMI) is associated with self-reported global life satisfaction, and if weight loss among individuals with overweight is associated with a higher life satisfaction than among weight-stable individuals with overweight. Methods: The participants in the present population-based cohort study from Denmark were 15,213 adults (18 years or older) in the Lolland-Falster Health Study who reported their global life satisfaction with the Cantril Ladder Score (CLS) (scores range from 0, very poor, through 10, very good). The association of BMI and history of weight loss with CLS was assessed by multivariable analyses adjusted for sex, age, educational level, cohabitation, self-reported health, and smoking status. Results: Higher BMI was associated with lower CLS (p < 0.0001). BMI 30–35 was associated with a 0.47 point (95% confidence interval [CI] 0.39; 0.55) lower score and BMI ≥45 with a 1.85 point (CI 1.45; 2.25) lower score, than BMI 18.5–25. History of weight loss was associated with lower CLS among individuals with BMI ≥25 (−0.15 lower CLS, p < 0.005), whereas in the subgroup of individuals with BMI ≥25 and good self-reported health, there was no significant difference in CLS between the weight stable and the weight loss groups (−0.05, p 0.33). Conclusion: This study found that higher BMI was associated with lower CLS. In subjects with BMI ≥25, weight loss was associated with lower CLS compared with stable weight during 5 years. In subjects with BMI ≥25 and good self-reported health, there was no relation between weight loss and CLS. Thus, contrary to our hypothesis, we found that weight loss among participants with overweight was not associated with higher life satisfaction.