This study aims to examine the impact of periodontal disease in obesity on COVID-19 infection and associated outcomes. This retrospective longitudinal study included 58,897 UK Biobank participants tested for COVID-19 between March 2020 and February 2021. Self-reported oral health indicators (bleeding gums, painful gums, and loose teeth) were used as surrogates for periodontal disease. Body fat levels were quantified by body mass index (BMI) and categorized as normal weight (18.5 to 24.9 kg/m2), overweight (25 to 29.9 kg/m2), and obese (≥30 kg/m2). Multivariable logistic regression and Cox proportional hazard models were used to quantify risk of COVID-19 infection, hospital admission, and mortality, adjusted for participants’ demographics and covariates. Of 58,897 participants, 14,466 (24.6%) tested positive for COVID-19 infection. COVID-19 infection was higher for participants who were overweight (odds ratio, 1.18; 95% CI, 1.12 to 1.24) and obese (odds ratio, 1.33; 95% CI, 1.26 to 1.41) as compared with those of normal weight, but infection was not affected by periodontal disease. The hospital admission rate was 57% higher (hazard ratio, 1.57; 95% CI, 1.25 to 1.97) in the obese group with periodontal disease than without periodontal disease, and admission rates increased with BMI category (normal weight, 4.4%; overweight, 6.8%; obese, 10.1%). Mortality rates also increased with BMI category (normal weight, 1.9%; overweight, 3.17%; obese, 4.5%). In addition, for participants with obesity, the mortality rate was much higher (hazard ratio, 3.11; 95% CI, 1.91 to 5.06) in participants with periodontal disease than those without. Obesity is associated with higher hospitalization and mortality rates, and periodontal disease may exacerbate this impact. The results could inform health providers, policy makers, and the general public of the importance to maintain good oral health through seamless provision of dental services and public oral health prevention initiatives.