Increased workload during the COVID-19 pandemic has threatened nurses’ mental health. This study aimed to identify factors associated with job stress in COVID-19 nurses compared to other nurses. Nurses were recruited from four hospitals in Republic of Korea in November 2020. The general sociodemographic questionnaire, job stress, anxiety (GAD-7), and depression (PHQ-9) were used to conduct an online survey. Stepwise multiple regression analysis was used to identify the factors associated with job stress. A total of 290 participants were analyzed: 122 in the dedicated ward and 168 in the nondedicated ward nurse groups. Job stress, anxiety, and depression were higher in nurses dedicated to COVID-19 (4.19 ± 0.59, 5.98 ± 3.92, and 6.97 ± 4.47, respectively) than in the nondedicated group (3.92 ± 0.72 (p= 0.001), 4.98 ± 4.20 (p= 0.042), and 5.92 ± 4.36 (p= 0.047), respectively). Among COVID-19 nurses, job stress levels were higher in 30–39 year olds than in 20–29 year olds (3.71 ± 0.43 vs. 4.04 ± 0.54,p= 0.006) and in non-smokers compared with smokers (3.85 ± 0.49 vs. 3.38 ± 0.53,p= 0.24). Anxiety (β = 0.34, standard error (SE) = 0.01,p< 0.001) and clinical experience of 5–10 years (β = 0.23, SE = 0.10,p= 0.004) were associated with job stress. These findings can be applied when devising response strategies for infectious diseases and developing psychological and organizational intervention programs for alleviating job stress in nurses.