Background: There is the scarcity of population-based studies on knowledge, attitude, and practice (KAP) about COVID-19 in Tamil Nadu and no literature on the rural-urban differences in KAP about COVID-19 in Tamil Nadu. Aims and Objectives: The study was conducted with the primary objective of estimating KAP regarding SARS-COV2 virus in Tamil Nadu and secondary objectives of determining the rural-urban differences in KAP and identifying the association between KAP and certain sociodemographic factors. Materials and Methods: An analytical cross-sectional study was done on 305 participants selected from the rural and urban population of Tamil Nadu. Urban data were collected using Google Forms through social media and the rural population data were collected through simple random sampling from three villages in the outskirts of Chennai District. The study tool had ten items to evaluate the knowledge, three items to evaluate the attitude and four items to evaluate the practice regarding COVID-19. Results: The overall KAP scores had a mean of 7.88 out of 10 (78.8%) for correct knowledge, 2.51 out of 3 (83.5%) for positive attitude, and 3.68 out of 4 (92%) for good practice. The knowledge score was slightly higher in the urban region, but the mean practice score (P ≤ 0.001) and attitude score (P < 0.001) were significantly more among the rural population. There was a statistically significant association between higher knowledge score and educational status (P = 0.0000001), male gender and better attitude (P = 0.0052) and higher age (>40 years) and better practice (P = 0.014). Conclusions: The study revealed reasonably good levels of KAP in regard to COVID-19 in Tamil Nadu in both the urban and rural populations.
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