Background: Multimorbidity is of increasing prevalence and importance. It has been negatively associated with health-related quality of life (HrQoL) especially in the elderly population. Despite substantial multimorbidity for the middle-aged population, defined as those between 40-64 years old, there is a paucity of research investigating the impact of multimorbidity in this population. This study aimed to investigate the association between multimorbidity and HrQoL in the middle-aged primary care population in Singapore.Methods: A cross-sectional study was conducted at a primary care centre in Singapore. Interviewer-administered questionnaires were used to collect data regarding the participants’ sociodemographic characteristics, chronic conditions, and HrQoL, as measured by the EuroQol five dimensions 3-levels questionnaire (EQ5D). We defined multimorbidity as the presence of three or more conditions, out of a list of 14 chronic conditions. The associations between multimorbidity and the components of the EQ5D were assessed using multivariable regression analyses.Results: The study included 297 participants, aged 40-64 years, of which 124 (41.7%) had multimorbidity. After adjusting for sociodemographic factors, participants with multimorbidity had significantly lower EQ5D UI, (β-coefficient -0.064 (C.I -0.125, -0.003), p = 0.04), but not significantly lower EQ5D VAS, (β-coefficient -0.045 (C.I 0.102, 0.012), p = 0.12). Additionally, participants with multimorbidity had higher odds (OR = 2.41, p = 0.01) of reporting problems due to pain/discomfort.Conclusion: Multimorbidity was not significantly associated with the overall health state, as measured by the EQ5D VAS, in middle-aged primary care patients. However, it was associated with the EQ5D UI which is a composite measure of five specific domains of HrQoL. Specifically, there was a statistically significant association between multimorbidity and the pain domain. Further studies are required to understand the relationship between multimorbidity and pain to enable physicians to better manage pain and HrQoL in this population.