Background <p>The EQ-HWB was developed to capture broader aspects of wellbeing beyond traditional health-related quality of life. However, empirical evidence from non-European populations remains limited. This study evaluated the psychometric performance of the EQ-HWB-9 utility index and the EQ-HWB profile measure in a large sample of the Japanese general population, with a focus on multimorbidity and depression.</p> Methods <p>We analysed data from a nationwide web-based cross-sectional survey (<i>n</i> = 5,177). The EQ-HWB-9 utility and EQ-HWB composite scores were examined across levels of multimorbidity and depression. Known-group validity was assessed using one-way ANOVA and independent-samples t-tests. Multivariable ordinary least squares regression with HC3 robust standard errors was used to estimate adjusted associations between the selected conditions and the EQ-HWB-9 utility.</p> Results <p>The EQ-HWB-9 utility scores decreased monotonically with increasing number of comorbid conditions. The respondents reporting depression had substantially lower EQ-HWB-9 utility scores (β = −0.124 (95% CI − 0.148 to − 0.101)) and markedly lower standardized EQ-HWB composite scores. In multivariable models adjusted for age, sex, and multimorbidity, depression, arthritis, and lower back pain were independently associated with lower EQ-HWB-9 utility scores. The EQ-HWB provides complementary descriptive information, highlighting multidimensional wellbeing deficits associated with depression.</p> Conclusions <p>These findings support the construct validity and known-group validity of the EQ-HWB in Japan. The EQ-HWB-9 captured both the cumulative multimorbidity burden and condition-specific impacts on wellbeing, particularly for depression, whereas the EQ-HWB offered broader profile-level insights. The EQ-HWB framework may be especially valuable for wellbeing assessment and economic evaluation in populations with a high prevalence of multimorbidity and depression.</p>