Background: Nicotine dependency would have increased during the times of COVID-19 among the primary health professionals, which would can be attributed to perceived stress and can also be influenced by self-efficacy; hence, the aim of the present study was to determine the relationship between nicotine dependence with perceived stress, self-efficacy among primary health care professionals during the times of covid-19 pandemic. Materials and Methods: The present study was a cross-sectional descriptive questionnaire study. The study was conducted among primary health workers of Ajmer district; stratified random sampling technique was used to collect data. A questionnaire was prepared that consists of demographic details, questions on perceived stress, self-efficacy, and nicotine dependence. Results: Perceived stress and nicotine dependence was high among study participants. Self-efficacy was low. There was significant ( P ≤ 0.05) association between high nicotine dependence and high perceived stress. It was also reported that majority of study participants {58 (30.4%)} with high self-efficacy significantly ( P ≤ 0.05) was associated with low nicotine dependence. Conclusion: High nicotine dependence was significantly associated with high perceived stress, while low nicotine dependence was significantly lower among primary health care workers’ low perceived stress. Low nicotine dependence was significantly associated among study participants with high self-efficacy.