Background: With the advent of the COVID-19 pandemic caused by SARS-CoV-2, protocols such as social distancing and upscaling of hygiene practices were implemented to limit the spread of the disease. Meanwhile, along with COVID-19 came stress due to restrictions on movement, trade and transport, and closure of schools, among others. Aim: This study compared the prevalence of hygiene-related gastrointestinal infections and stress-related diseases before (March 2019–February 2020) and during (March 2020–February 2021) the COVID-19 pandemic. Methodology: This was a retrospective single-center review of deidentified patient data from the Korle Bu Polyclinic, Accra, Ghana. Results: Comparing the pre-COVID-19 era to the COVID-19 era, there was a statistically nonsignificant change in the number of cases and prevalence of gastroenteritis and enteric fever (p = 0.084 and 0.081, respectively), although for gastroenteritis, the prevalence was higher for the pre-COVID-19 era compared to during COVID-19 by 1.8 per 1000 cases, while that of enteric fever was higher during the COVID-19 era compared to the pre-COVID-19 era by 1.0 per 1000 cases. Of the stress-related diseases, statistically significant increases in the prevalence of anxiety disorders (p = 0.028), insomnia (p = 0.001), and headache (p = 0.010), were noted, with 2.3, 5.5, and 2.4 per 1000 cases, respectively. There were more female cases than male cases recorded for depression (p = 0.001), headache (p = 0.010), and hypertension (p = 0.001) during the pandemic, and these were statistically significant. Conclusion: During the pandemic, a significant increase in the prevalence of stress-related diseases was observed. However, a statistically nonsignificant change was recorded for gastrointestinal infections, with females reporting more of these disorders. Consequently, it is important to strengthen the capacity for managing stress-related conditions alongside diseases that cause pandemics when they arise.