Background: The coronavirus disease-2019 (COVID-19) pandemic, and the lockdown imposed, has had profound social and economic consequences and thereby implications on psychological health. This study aims to understand the effects of the pandemic and the lockdown on the prevalence, spectrum, and outcome of patients presenting with deliberate self-harm (DSH) to the emergency department (ED). Materials and methods: This was a retrospective, observational study done in the ED of a tertiary care hospital in South India on DSH victims presenting from January to August 2020, spanning the prelockdown, lockdown, and unlock phases of the pandemic, and compared with data from a similar period in 2018. Results: Our study population included 507 DSH victims (prevalence: 1.2%) from January to August 2020. The percentage of DSH cases showed a slight increase among the prelockdown (203/17,234: 1.18%), the lockdown (179/14,687: 1.22%), and the unlock phases (125/9,977: 1.25%). There was a female preponderance (286/507: 56.4%), and the mean age was 33.2 years. Of the 507 patients, 369 (72.8%) were admitted and 19 (3.7%) died. The lockdown period in 2020 showed a 40.9% absolute decrease in the number of DSH victims presenting to the ED as compared to an equivalent period in 2018. The proportion of patients taking plant poisons was significantly lower [odds ratio (OR) 0.38, 95% confidence intervals (CI) 0.18–0.81, p = 0.012] and that of corrosive ingestion was significantly higher (OR 2.94, 95% CI 1.57–5.48, p = 0.001) in the lockdown phase as compared to a lockdown-control phase of 2018. Conclusion: There was a reduction in the absolute number of patients presenting with DSH to the ED during January–August 2020, and more so during the lockdown phase (March 24–June 30), as compared to a similar period in 2018. There was no significant difference in the hospital outcome of DSH patients between the two periods.