Objectives An overlap between the somatic symptoms of depression and those of uremia seen in end-stage renal disease (ESRD) patients may affect the diagnosis of depression. This study aims to evaluate the effect of hemodialysis on the diagnosis of depression among patients on maintenance hemodialysis as dialysis diminishes the uremic symptoms, and to compare depression scores before and after dialysis. Methods This was a cross-sectional analytic study conducted from November 2018 through April 2019, in three tertiary hospitals. Consenting participants aged 18 years or older, who had received hemodialysis for at least three months were included. The Patient Health Questionnaire (PHQ-9) tool was used to collect patients’ data and to identify symptoms of depression Pre- and post-hemodialysis. Depression scores were compared using the paired sample Wilcoxon rank test or the McNemar test, where appropriate. Results Overall, 163 participants were enrolled in the study. The average age of the participants was 56.5 years old, whereas 44.8% were females. The prevalence of depressive symptoms before hemodialysis was 48.5%, with prevalence of mild, moderate and moderately severe of 34.4%, 11.7% and 2.5%, respectively. On the other hand, the prevalence of depressive symptoms after hemodialysis was 46.6% with 36.8%, 9.2% and 0.6% of the participants reporting mild, moderate and moderately severe symptoms, respectively. We found no significant difference in depression scores before and after dialysis (p-values > 0.05). Conclusion Our study supports the fact that the prevalence of depression is high among patients with ESRD on maintenance hemodialysis. We didn’t find a significant difference in depression scores among hemodialysis patients before and after dialysis, with negligible effect of uremic symptoms on the diagnosis of depression. We suggest adopting routine screening of depression among this high-risk group of patients.