This study aimed to compare qualities of major depression among people with prior COVID-19 illness and those without prior illness using a Qualtrics survey. People 18 years and older were included in the study from May 2020 to Feb 2021. Results revealed that of the 91,791 people who answered the Patient Health Questionnaire to measure depressive symptoms, associations with prior COVID-19 infection were found for income (z = 9.75; P < .001), sex (z = −9.58; P < .001), urban vs rural (z = 2.89; P = .004), and Black vs White (z = 3.02; P = .003). The largest difference in the questionnaire scores for people with prior COVID-19 illness and those without, were observed in motor symptoms (mean [SD], 2.58 [1.01] vs 2.11 [1.06]; t = −23.74; P < .001) and suicidality (mean [SD], 2.50 [1.06] vs 1.99 [1.09]; t = −24.83; P < .001). The authors suggest that people with prior COVID-19 illness may experience unique major depressive symptoms than those normally seen in adult patients. Additional research is needed to understand how major depressive symptoms among patients with prior COVID-19 illness differ or are similar to patients with major depressive disorders.