Objective: Exacerbated inflammatory pathway has emerged as a predominant etiological construct of major depressive disorder (MDD). Innate immune molecules like complement proteins induce inflammatory responses and also regulate key neurobiological processes. However, there is a dearth of literature on the impact of critical complement proteins in MDD. Herein, plasma profiling of seven complement proteins was carried out to obtain a better insight into the role of the complement pathway in MDD. Methods: Plasma levels of C1q, C3, C3b/iC3b, C4, Factor B, Factor H, and properdin were assayed in 22 patients with MDD and 27 healthy controls by multiplex suspension assay. The patients with MDD were diagnosed as per DSM IV-TR. Hamilton Depression Rating Scale (HAM-D), Montgomery Depression Rating Scale and Clinical Global Improvement were used for clinical assessments of the patients. The plasma levels of these complement proteins were also correlated with various clinical scores and phenotypes of MDD. Results: The patients with MDD and healthy controls did not differ in terms of age and gender (p ＞ 0.1). The patients with MDD had a mean duration of illness of around 3 years, with average number of depressive episodes being 6 and the mean HAM-D score was 19. Of the seven complement components, the plasma levels of C1q, Factor B, and Factor H (p ≤ 0.05) were significantly elevated in MDD patients compared to healthy controls. However, the plasma levels of these complement proteins were not found to correlate with the clinical profile of MDD patients. Conclusion Both Factor B and Factor H are crucial in the induction and regulation of the alternative pathway of complement activation. The alternative pathway also plays a critical role in inflammation. These findings suggest an important role of the alternative complement pathway in immuno-inflammation in MDD.