Background Studies show contradictory results on telework and MSDs, recommending investigating ergonomic factors and considering mental workload and inactivity. Objective To analyze the predictive association of mental workload, postural overload, and physical inactivity on the presence of MSDs in university professors in a pandemic context. Methods A pilot cross-sectional study. An online self-administered questionnaire was used with the Nordic Musculoskeletal Questionnaire (NMQ) to assess MSDs, the NASA-Task Load Index (NASA-TLX) for mental workload, The Rapid Office Strain Assessment (ROSA) to quantify ergonomic risks, and a physical activity question. The data obtained were analyzed by descriptive statistics and the association between the independent and dependent variables by Chi-square and logistic regression with an α = 0.05. Results Fifty-one university professors (58.8% female) participated. The frequency of MSDs was 82.3% and was most common in the neck region (62.7%). Significant associations of mental workload, postural overload, and physical inactivity on MSDs were found. Multiple predictive associations were observed between MSDs in the wrists and hands, chair postural overload, and physical inactivity (OR = 11.84 and OR = 15.38, respectively) while considering confounding variables such as gender, age, and BMI. In addition, MSDs in the upper back were observed with chair and mouse-keyboard postural overload (OR = 5.60 and OR = 7.59, respectively). Conclusions Predictive associations exist between mental workload, postural overload, physical inactivity, and MSDs. In the post-COVID era, teleworking has become essential in universities, and it is crucial to plan for it to prevent the risk of musculoskeletal disorders.