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Key Points Question What are the risk factors associated with SARS-CoV-2 infection among farmworkers in California? Findings In this cross-sectional study of 1107 farmworkers, both household and workplace risk factors, including living with children aged 5 years or younger or unrelated roommates and living or working with an individual with known or suspected COVID-19, were associated with positive results on transcription-mediated amplification tests and immunoglobulin G tests for SARS-CoV-2 infection. Meaning These findings suggest that urgent distribution of vaccines to farmworkers and intervention on modifiable risk factors for SARS-CoV-2 infection are warranted given this population’s increased risk and the essential nature of their work., This cross-sectional study identifies risk factors associated with SARS-CoV-2 infection among farmworkers in California., Importance Essential workers in agriculture and food production have been severely affected by the ongoing COVID-19 pandemic. Objective To identify risk factors associated with SARS-CoV-2 infection among farmworkers in California. Design, Setting, and Participants This cross-sectional study invited farmworkers in California’s Salinas Valley (Monterey County) receiving transcription-mediated amplification (TMA) tests for SARS-CoV-2 infection at federally qualified community clinics and community sites to participate. Individuals were eligible if they were not pregnant, were 18 years or older, had conducted farmwork since the pandemic started, and were proficient in English or Spanish. Survey data were collected and SARS-CoV-2 tests were conducted among participants from July 16 to November 30, 2020. Exposures Sociodemographic, household, community, and workplace characteristics. Main Outcomes and Measures TMA- and immunoglobulin G (IgG)–positive SARS-CoV-2 infection. Results A total of 1107 farmworkers (581 [52.5%] women; mean [SD] age, 39.7 [12.6] years) were included in these analyses. Most participants were born in Mexico (922 [83.3%]), were married or living with a partner (697 [63.0%]), and worked in the fields (825 [74.5%]). Overall, 118 of 911 (13.0%) had a positive result on their TMA test for SARS-CoV-2 infection, whereas 201 of 1058 (19.0%) had antibody evidence of infection. In multivariable analyses accounting for recruitment venue and enrollment period, the incidence of TMA-positive SARS-CoV-2 infection was higher among those with lower than primary school–level education (adjusted relative risk [aRR], 1.32; 95% CI, 0.99-1.76; non–statistically significant finding), who spoke an Indigenous language at home (aRR, 1.30; 95% CI, 0.97-1.73; non–statistically significant finding), who worked in the fields (aRR, 1.60; 95% CI, 1.03-2.50), and who were exposed to a known or suspected COVID-19 case at home (aRR, 2.98; 95% CI, 2.06-4.32) or in the workplace (aRR, 1.59; 95% CI, 1.18-2.14). Positive results on IgG tests for SARS-CoV-2 infection were more common among those who lived in crowded housing (aRR, 1.23; 95% CI, 0.98-1.53; non–statistically significant finding), with children aged 5 years or younger (aRR, 1.40; 95% CI, 1.11-1.76), with unrelated roommates (aRR, 1.40; 95% CI, 1.19-1.64), and with an individual with known or suspected COVID-19 (aRR, 1.59; 95% CI, 1.13-2.24). The risk of IgG positivity was also higher among those with body mass index of 30 or greater (aRR, 1.65; 95% CI, 1.01-2.70) or diabetes (aRR, 1.31; 95% CI, 0.98-1.75; non–statistically significant finding). Conclusions and Relevance In this cross-sectional study of farmworkers in California, both residential and workplace exposures were associated with SARS-CoV-2 infection. Urgent distribution of COVID-19 vaccines and intervention on modifiable risk factors are warranted given this population’s increased risk of infection and the essential nature of their work.