Background: A cure for the heterogeneous hematological malignancy multiple myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM have not been fully elucidated. Studies have shown an aberrant complement system in patients with MM, but the precise association necessitates elucidation. Therefore, this study scrutinizes the correlation between serum complement level and the disease outcome of patients with MM. Methods: A retrospective analysis of 72 patients with MM (new diagnosis) with complement C4 and C3 along with common laboratory indicators was done. The Pearson χ2 test and the Mann-Whitney U-test were done to evaluate categorical or binary variables and intergroup variance, respectively. Kaplan-Meier test and Cox proportional hazards regression were used for quantification of overall survival (OS) and univariate or multivariate analyses, respectively. Results: The Cox proportional hazard model analysis unveiled the following: platelet ⩽115.5 × 109/L (hazard ratio [HR] = 5.82, 95% confidence interval [CI] = 2.522-13.436, P <0.001), complement C4 ⩽0.095 g/L(HR = 3.642, 95% CI = 1.486-8.924, P = .005), age ⩾67 years (HR = 0.191, 95% CI = 0.078-0.47, P <0.001), and bone marrow plasma cell percentage ⩾30.75% (HR = 0.171, 95% CI = 0.06-0.482, P = 0.001) can be used as independent predictors of OS. Of these, advanced age, low platelet level, and a high proportion of bone marrow plasma cells have been implicated in poor outcomes in patients with MM. Interestingly, a low complement 4 level can function as a new indicator of poor prognosis in patients with MM. Conclusion: Low levels of C4 are indicative of a poor outcome in newly diagnosed patients with MM.