Background: Although, the relation between inflammation and major depressive disorder (MDD) looks like firm, it may not exist in all patients with depression. Therefore, the main aim of this study was to compare serum Creactive protein (CRP) level among clinical subtypes of MDD and its relation with suicidality. Results: According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD, 98 patients included and categorized into five clinical subtypes groups: atypical, anxious, melancholic, psychotic, and unspecified depression with percent (11.2%, 31.6%, 19.4%, 15.3%, and 22.4%) respectively. Twentyfour (24.5%) of all patients had suicidal thoughts using Beck Scale for Suicidal Ideation (BSS) with statistically significant increase (P < 0.05*) in suicidality among atypical group. On assessing CRP level, there was highly statistical significant increase (P < 0.001**) among cases with atypical type and also cases with suicidal ideation. Also, logistic regression analysis found that the significant predictors for high CRP among the studied cases were smoking, suicidality, atypical depression, and suicide depression. Conclusions: Higher level of CRP was found among patients with atypical MDD, and there was significant relationship between CRP and suicidality.