Background: COVID-19 has been recognized as a pandemic by the World Health Organization. originated from China and has rapidly crossed borders, infecting people throughout the whole world. The present study sought to determine knowledge, attitude and behavior (KAB) of South Indian population toward COVID-19 Quarantine. Methods: An online cross sectional, semi-structured questionnaire was undertaken through google forms among South Indian population (SIPs). SIPs aged 18 years and above constituted the study population. Data was analyzed using SPSS Software Results: Totally 280 responses were received. The responders had a moderate level of knowledge about the COVID-19 infection and adequate knowledge about its preventive aspects. The attitude towards COVID-19 showed peoples' willingness to follow government guidelines on quarantine and social distancing. 32% of Participants have felt stressed during quarantine and 32.4% of participant had sleep disturbance. Alarmingly 32% are not anxious and feel free to roam around in public places without protective measures like mask and gloves. In this study, panic about acquiring COVID-19 infection during purchase and travel were reported in 29.5% and 11% participants respectively. The perceived Physical healthcare need was seen in more than 69% of participants. Conclusions: COVID-19 Quarantine knowledge is gained mainly through media channels, Newspaper, which have strengths and weaknesses. Although the government has taken major steps to educate the public and limit the spread of the disease, there is a need to intensify the alertness of people during this COVID-19 Quarantine.