The impact of the COVID-19 pandemic and lockdown may affect suicide risk and behavior. We compared suicide-related presentations during the national quarantine with pre-COVID data. This observational incidence study compared all suicide-related presentations at the University Hospital Reina Sofia emergency department (ED) in Cordoba, Spain, for the lockdown period from 15 March to 15 May 2020, with the same period in 2019. Descriptive and inferential analyses of case characteristics between 2019 and 2020 periods were conducted, and a multivariable logistic regression model developed. Results: Despite a decrease in overall ED cases during the lockdown, the number of suicide-related presentations stayed the same and represented a significantly larger proportion of cases in comparison to the pre-COVID period (0.42 vs. 0.87%, in 2019 and 2020, respectively; p < .001). The number presenting alone more than doubled during the COVID lockdown, increasing to 42.9% compared with 19.4% in 2019 (p = .002). An increase in presentations with a family history of suicide was also found. Conclusions: Suicide cases represented an increased proportion of ED cases during the lockdown. Presenting to ED alone, having a family history of suicide, habitual drug consumption, and hospital admission to ICU differentiated cases between pre and during COVID periods. These findings should be considered in light of the second wave and further implementation of lockdown measures.