Sexual and gender minority (SGM) college students experience compounding psychological effects as a result of the COVID-19 pandemic. Using latent profile analysis of cross-sectional data from a sample of SGM students (n=565) we tested for a syndemic of victimization, internalized LGBTQ+ stigma, racism, racialized heterosexism/cisgenderism, family rejection, and isolation associated with psychological distress. We also tested if increases in these factors since the start of the COVID-19 pandemic were associated with greater psychological distress among syndemic profiles. We identified four profiles: "Lowest syndemic factors" (reference), "High isolation only," "High isolation and rejection only," and "High syndemic." The greatest distress was observed among the "High syndemic" profile (aPR=2.99, 95% CI 2.20, 4.06), followed by the "High isolation and rejection only" profile (aPR=2.11, 95% CI 1.61, 2.76), and the "High isolation only" profile (aPR=1.32, 95% CI 1.03, 1.70). Among the "High syndemic profile," increases in every factor since the start of the COVID-19 pandemic were associated with greater psychological distress. The strongest associations were seen among increased victimization (aPR=5.85, 95% CI 1.33, 25.71). Victimization, internalized LGBTQ+ stigma, racism, family rejection, and isolation form a syndemic among SGM students, which has magnified since the start of the COVID-19 pandemic.