Background: The common illness known as Major depressive disorder (MDD) is defined by significantly increased rates of illness and disease, impairment, and suicidal thoughts. Numerous investigations have demonstrated the significant impact cystatin C plays in cognitive impairment and major depressive disorder (MDD).

Aim: To assess the relation between serum cystatin c concentration and depressive symptoms, suicidal ideation and cognitive dysfunctions in patients with MDD.

Methods: Our case–control study was carried out on 69 patients with major depressive disorder diagnosed according to DSM-V criteria that attended outpatient clinic of the Psychiatry department El-Azazy psychiatric hospital & Psychiatry department at Zagazig university hospitals and 69 healthy controls. Cystatin C level was measured.

Results: Cystatin C level was significantly higher in major depression patients compared to controls. There was a significant positive correlation between cystatin C with age, Hamilton depression rating scale, BECK scale and MOCA scale. Cases in rural areas showed significant elevation in cystatin C level compared to cases in urban areas (p=0.025). There was a significant relation between degree of depression, suicidal ideation, cognitive dysfunction and cystatin C as it was significantly higher in these cases. Cystatin C was a significant predictor of major depressive disorder (AUC=0.851, P value<0.001). The suggested cut-off value (>1 mg/L) showed 66.7% sensitivity, 92.8% specificity, 90.3% PPV and 73.6% NPV

Conclusion: Serum Cys C levels are associated with depressive symptoms, cognitive dysfunction and suicidal ideation in MDD patients.