Background: COVID19 pandemic forced most countries to lockdown, leading to the prolonged closure of many learning institutions. This dramatic shift led to increase of mental illness symptoms among university students. Objective: To determine the prevalence and factors associated with symptoms of depression, anxiety, and stress among Uganda’s university students during the COVID-19 lockdown. Methods: We conducted a one-month online survey using the Depression Anxiety and Stress Scale (DASS-21). Results: Participants n=321 were enrolled with mean age, 24.8(SD=5.1) years and 198(61.7%) were males. The prevalence of mental health symptoms among participants was 80.7%, 98.4%, and 77.9% for depression, high levels of anxiety,and stress, respectively. Statistically significant association between mental health symptoms on multi-logistic regression was found with Males (depression=2.97[1.61–5.48] and stress=1.90[1.07–3.35]), engagement in leisure activity (depression= 1.87[1.01–3.49] and stress=1.98[1.10–3.56]), and being finalist (stress=0.55[0.31– 0.97]). Use of addictive substances seem to potentially alleviate symptoms of depression, anxiety and stress in the short term.  Conclusions: The findings of this study suggest a high prevalence of symptoms of depression, anxiety and stress among university students during the COVID-19 lockdown. Students’ mental health should be monitored by all stakeholders, especially as the pandemic progresses. Keywords: COVID-19 lockdown; University students; Mental health.