The pandemic caused by Covid-19 has led university students in Mexico to take their classes online, where they have to interact with furniture and computer equipment different from the one that exists in classrooms. Interaction with such furniture and equipment can be uncomfortable and have an impact on the students’ Academic performance. Therefore, this article aims to determine the impact of Desk / Table design, Chair design, and Human-computer interaction (antecedent variables), as well as the Mental workload (mediating variable) on university students’ Academic performance (consequent variable) during the Covid-19 pandemic. A questionnaire is developed and applied online to 167 university students, and three mediation models were built where seven hypotheses are included. These hypotheses were statistically validated by applying the ordinary least squares regression algorithm. The results indicated that the three antecedent variables have a significant direct effect as well as total effects of 0.21, 0.14, and 0.49, respectively, while total effects of 0.22, 0.17, and 0.49 on the university students’ Academic performance. The indirect effects were negligible. It is suggested that the three antecedent variables play an essential role in the sustainability of university students.