The contribution of pre-existing conditions to severe versus mild postacute sequelae (PASC) of SARS-CoV-2 in the population is lacking. Here, we evaluated reproductive and other PASC side-by-side in unvaccinated and vaccinated individuals after 1st SARS-CoV-2 infection. In an online global survey of 7,541 individuals from 95 countries, high grade fever (> 102˚F)/ hospitalization after a first SARS-CoV-2 infection were more likely to be reported by vaccinated males than unvaccinated males (13.64% vs. 8.34%; p = 0.0483; HR = 1.63 [95% CI: 1.008, 2.65]). Women reported experiencing more frequent PASC than men. More women than men reported vaccine-associated adverse events (AEs) after the 1st dose (60.85% vs 48.79%, p < 0.01). Vaccine-associated hospitalization was reported by 6.24% SARS-CoV-2 naïve respondents versus 1.06% of unvaccinated after 1st SARS-CoV-2 infection. Pre-existing thyroid disease, osteoporosis, and autoimmune disorders were more prevalent in women, whereas more men reported back problems, elevated cholesterol, and hypertension; several pre-existing conditions posed ≥ 2.0 relative risk of developing severe vs mild COVID-19. Individuals aged < 55 years had an absolute risk of 6.01%, whereas individuals ≥ 55 years had an absolute risk of 11.69% of getting severe vs mild COVID-19 disease. Vaccinated women reported significantly greater menstrual cycle-associated reproductive PASC compared to unvaccinated women. Vaccinated men reported hormonal changes and sexual dysfunction as reproductive PASC compared to unvaccinated men. A detailed and thorough follow-up is needed to better understand if pre-existing health conditions and/or vaccine-associated AEs exacerbated COVID-19 sequelae.