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Introduction: It is well-recognized that containing COVID-19 successfully is determined by people’s prevention measures which are related to their knowledge, attitudes, and practices (KAP). This perception has attracted attention in low- and middle-income countries (LMIC) due to their fragile health systems and economies. The objective of this study was to understand how residents in Malawi perceived COVID-19, to determine the factors related to KAP. Methods: A semi-structured questionnaire was used for the data collection. A field-based survey was conducted among adult residents in Lilongwe, Malawi. Descriptive statistic, linear regression, the Chi-square test, and Pearson’s correlation statistics were used for data analysis. Results: A total of 580 questionnaires were involved. The mean knowledge, attitude, and practice (KAP) scores were 10 (SD = ±3, range: 3–19), 16 (SD = ±4, range: 5–25), and 2 (SD = ±1, range: 0–5), respectively. Lack of money and resources (39%) was the biggest challenge for people who practice prevention measures. Among the participants, the radio (70%) and friends/family (56%) were the main sources of information. A higher economic status was associated with better KAP. Conclusions: A low level of KAP was detected among the population. The people faced challenges regarding a lack of necessary preventive resources and formal information channels. The situation was worse considering vulnerable population who had low economic status. Further all-round health education is urgently needed along with providing adequate health supplies and ensuring proper information management.