Background: Hand eczema, in time of COVID-19, is one of the most frequently diagnosed skin disorders in nurses. In this study, we sought to investigate whether smoking could be an additional risk factor for hand eczema in nurses during the COVID-19 pandemic. Method: Using a questionnaire about smoking details and hand eczema, we conducted a study among nurses involved in the frontline management of COVID-19 patients. A total of 1,000 questionnaires were sent out. The questionnaires were anonymous and based on self-reported answers, with no clinical examination or medical data evaluation. All nurses enrolled in the study were women, working in shifts for the last three months since the start of the COVID-19 pandemic. Results: Two-hundred forty-seven questionnaires were accepted for the study, after eliminating non-responders and nurses without hand eczema. The majority of nurses denied smoking (87.85%) in the past and at the moment of the study. Statistics related to years of smoking and occurrence of hand eczema showed no increase in the number of cases in correlation with the number of years of smoking. Similarly, a random distribution of cases of hand eczema was observed when compared to the number of cigarettes per day. Conclusion: Our data does not support the hypothesis that smoking is an independent risk factor for the development of occupational hand eczema during the COVID-19 pandemic.