ObjectiveWe examined the impact of language preference and health literacy on health information-seeking experiences in a multilingual, low-income cohort. MethodsWe administered a modified Health Information National Trends Survey in English, Spanish, and Chinese to a sample of San Francisco city/county residents. Using multivariable logistic regression analyses, we assessed how language and health literacy impact health information-seeking experiences (confidence, effort, frustration, quality concerns, and difficulty understanding information), adjusting for age, gender, race/ethnicity, education, usual place of care, health status, information-seeking behaviors, and smartphone ownership. ResultsOf 1000 participants (487 English-speaking, 256 Spanish-speaking, 257 Chinese-speaking), 820 (82%) reported at least one negative health information-seeking experience. Chinese-language was associated with frustration (aOR = 2.56; 1.12–5.86). Difficulty understanding information was more likely in Spanish-language respondents (aOR = 3.58; 1.25–10.24). Participants with limited health literacy reported more effort (aOR = 1.97; 1.22–3.17), frustration (aOR = 2.09; 1.28–3.43), concern about quality (aOR = 2.72; 1.60–4.61), and difficulty understanding information (aOR = 2.53; 1.58–4.05). Language and literacy impacted confidence only in the interaction term between Chinese-speakers and health literacy. ConclusionWe found that negative health information-seeking experiences were common in non-English speaking populations those with limited health literacy. Practice implicationsHealth communication efforts should consider both language preference and health literacy to ensure accessibility for all patients.