This study was designed to investigate the effects of 8 weeks of weight-bearing resistance exercise on physical fitness, musculoskeletal symptoms, and stress indices in female call center employees. Twenty-two subjects, aged 40s to 50s, were randomly assigned to one of two groups, i.e., weight-bearing resistance exercise group (TR; n=11) and control group (CON; n=11). Subjects in the TR participated in weight-bearing resistance exercise 30 min/session, 3 sessions/week for 8 weeks, whereas subjects in the CON were asked to maintain their normal life patterns during the same period of the intervention. Dependent variables regarding physical fitness, musculoskeletal symptom, and stress were measured and compared between two groups and between two tests simultaneously using a repeated two-way ANOVA. Main results of the present study were as follows: 1) Muscular endurance, flexibility, balance, muscular power, and cardiorespiratory endurance improved significantly in the TR. 2) Number of musculoskeletal symptoms in neck, shoulder, and wrist reduced significantly in the TR. 3) Score of functional movement screen (FMS) increased significantly in the TR. 4) Scores of the Center for Epidemiologic Studies Depression (CES-D) scale, the Korean Occupational Stress Scale (KOSS), and the Perceived Stress Scale (PSS) decreased significantly in the TR. In addition, hs-CRP tended to decrease in the TR. It was concluded that 8 weeks of weight-bearing resistance exercise would be beneficial for improving physical fitness, reducing work-related musculoskeletal symptoms, and relieving stress in female call center employees.