Background: Effective management of the spread of a novel infectious disease, such as the COVID-19 virus can be achieved through influencing people’s behavior to adopt preventive measures. The public’s perceptions and attitudes towards the virus, governmental guidance and preventive measures were unknown in Saudi Arabia. Objectives: Identify the anxiety level, risk perception, information sources, adoption of preventive measures, and ability and willingness to self-isolate during and post-lockdown periods of the COVID-19 pandemic. Investigate socio-demographic factors associated with adoption of preventive measures against COVID-19 and self-isolation.Method: Between April 22nd and June 21st 2020, Saudi adults aged ≥18 years completed an open web-based survey including questions on anxiety level, COVID-19 risk perceptions and adoption of preventive measures. Weighted percentages, Pearson’s chi-square tests, and multiple logistic regression were applied to evaluate associations between these factors and socio-demographic variables. Results: A total of 2,393 respondents filled-out the survey with around (27.2%) aged 35-44 years old. Around 11% of the respondents reported high anxiety level, 74% were worried about the COVID-19 outbreak, and of those, 27% reported that it is likely that they will be infected with COVID-19 with 16% believing it will be life-threatening or severe. Adoption of hygiene practices and social distancing were lower among older (65+ years) compared to younger (18-24 years) respondents (OR: 0.06; 95% CI: 0.01, 0.28, OR 0.06; 95% CI: 0.01, 0.27), respectively. Around 88% reported being able and 82% willing to self-isolate. Those with the lowest gross household income and those with at least one flu symptom were less able and willing to self-isolate. A significant increase was reported in levels of anxiety, perceived effectiveness of social distancing and hygiene practices in the post-lockdown period compared to the lockdown. Conclusions: The study reported high levels of adoption of preventive measures and willingness and perceived ability to self-isolate during the early phase of the pandemic. Vulnerable groups such as the elderly, and those with low socio-economic status reported lower adoption of preventive measures or ability and willingness to self-isolate. Tailored public health messages and interventions are needed to achieve high adherence to these preventive measures in these groups.