To define the association between oral and systemic manifestations of Sjӧgren's syndrome (SS) and quality of life.We analyzed a cross-sectional survey conducted by the Sjӧgren's Foundation in 2016, with 2961 eligible responses. We defined oral symptom and sign exposures as parotid gland swelling, dry mouth, mouth ulcers/sores, oral candidiasis, trouble speaking, choking or dysphagia, sialolithiasis or gland infection, and dental caries. Systemic exposures included interstitial lung disease, purpura/petechiae/cryoglobulinemia, vasculitis, neuropathy, leukopenia, interstitial nephritis, renal tubular acidosis, autoimmune hepatitis, primary biliary cholangitis, or lymphoma. Outcomes included SS-specific quality of life questions generated by SS experts and patients.Using multivariable regression models adjusted for age, sex, race, and employment, we observed that mouth ulcers or sores, trouble speaking, and dysphagia were associated with poor quality of life. The following oral aspects had the greatest impact on these following quality of life areas: i) mouth ulcers/sores on the challenge and burden of living with SS (odds ratio [OR] 4.26, 95% confidence interval [CI] 2.89- 5.48), ii) trouble speaking on memory and concentration (OR 4.24, 95% CI 3.28-5.48), and iii) dysphagia on functional interference (OR 4.25, 95% CI 3.13-5.79). In contrast, systemic manifestations were associated with quality of life to a lesser extent or not at all.Oral manifestations of SS, particularly mouth ulcers or sores, trouble speaking, and dysphagia, were strongly associated with worse quality of life. Further study and targeted treatment of these oral manifestations provides the opportunity to improve quality of life in patients with SS.