Abstract Background During infectious disease outbreaks the weakest communities are more vulnerable to the infection and its deleterious effects. In Israel, the Arab and Ultra-Orthodox Jewish communities have unique demographic and cultural characteristics that place them at risk for infection. Objective To examine the socioeconomic and ethnic differences in relation to COVID-19 testing, cases and deaths, and to analyze infection spread patterns in ethnically diverse communities. Methods Consecutive data on COVID-19 diagnostic testing, confirmed cases and deaths collected from March 31 st through May 1 st , 2020 in 174 localities across Israel (84% of the population) were analyzed by socioeconomic ranking and ethnicity. Findings Tests were performed on 331,594 individuals (4·29% of the total population). Of those, 14,865 individuals (4·48%) were positive and 203 died (1·37% of confirmed cases). The percentage of the population tested was 26% and the risk of testing positive was 2·16 times higher in the lowest, compared with the highest socioeconomic category. The proportion of confirmed cases was 4·96 times higher in the Jewish compared with the Arab population. The rate of confirmed cases in 2 Ultra-Orthodox localities increased relatively early and quickly. Other Jewish and Arab localities showed consistently low rates of confirmed COVID-19 cases, regardless of socioeconomic ranking. Interpretation Culturally different communities reacted differently to the COVID-19 outbreak and to government measures, resulting in different outcomes. Therefore, socioeconomic and ethnic variables cannot fully explain communities’ reaction to the pandemic. Our findings stress the need for designing a culturally adapted approach for dealing with health crises.