<p>The spread of COVID-19 became the main public health risk for most countries in 2020. In Spain, emergency lockdown measures were imposed. Given this sudden situation, we tested the levels of risk perception, the psychological impact of isolation conditions and of coping behaviors. A total of 1343 adult residents in Spain participated in the study. We measured with an online questionnaire (a) risk perception; (b) individual, social, and physical conditions of isolation; and (c) a set of coping behaviors. We tested how the conditions of isolation and the individual behavior affected positive and negative affect and meaning in life. We observed that risk perception was directly linked with the individual and social situation of the participants. Personal resilience, employment status, profile of cohabitants, and using open air spaces in the house are linked with the emotional situation of the participants. Additionally, we found that some behaviors were related with positive affect, meaning in life, and negative affect. The psychological impact of a nation-wide lockdown is not universal and there are key factors that moderate this impact. We have identified key personal, behavioral, social, and physical factors that may help critical isolation situations.</p>