Background: Depression is a prevalent mood disorder characterized by persistent sadness and a lack of interest in activities, significantly impacting daily life. It is often accompanied by suicidal behavior, and inflammation markers like high-sensitivity C-reactive protein (hs-CRP) have been linked to its severity. Escitalopram, a selective serotonin reuptake inhibitor (SSRI), is commonly used in treating major depressive disorder (MDD). Method: This prospective interventional study was conducted at Mahatma Gandhi Memorial Medical College and MY Hospital, Indore, over 18 months. It involved 60 adult patients diagnosed with depression and suicidal behavior, as per ICD-10 criteria. Participants were drug-naïve or drug-free for three months prior to the study. The study assessed changes in hs-CRP levels and depression severity using the Hamilton Depression Rating Scale (HAM-D) before and after four weeks of escitalopram treatment. Results: The study found a significant reduction in hs-CRP levels from baseline (1.10 ± 0.97 mg/L) to the fourth week (0.91 ± 0.038 mg/L) post-treatment (p < 0.001). Depression severity also decreased significantly, as indicated by HAM-D scores dropping from 25.26 ± 5.937 at baseline to 14.78 ± 4.720 at the fourth week (p < 0.001). These reductions were consistent across various demographic groups, including age, gender, marital status, and education level. Conclusion: Escitalopram effectively reduces hs-CRP levels and alleviates depressive symptoms in patients with suicidal behavior. The reduction in hs-CRP levels is independent of its antidepressant effects, suggesting potential anti-inflammatory benefits of escitalopram in treating depression.