The COVID-19 outbreak forced Italian students to reduce their daily activities, inducing a seden-tary attitude that was worsened by distanced learning. This study aimed to survey the physical activity levels that were maintained before and during the social restrictions following the pan-demic, their correlation to musculoskeletal pain, as well as analyzing the impact of these COVID-19 restrictions on pain and fatigue that affects daily life activities. A total of 2044 students completed the online questionnaire, of which the results of 1654 participants were eligible. Before the pandemic, the levels of physical activity were distributed as: 19.9% no activity, 30.1% light ac-tivity, 21.5% moderate activity, and 28.5% high activity. After one year of the pandemic, 30.6% of the participants were inactive, 48.1%, 10.9%, and 10.5% stated as maintaining, respectively, light, moderate and high levels of physical activity. Furthermore, 43.5% reported neck pain and 33.5% stated to experience low back pain. Physical activity levels lower than 150 min/week may have predisposed students to suffer from neck pain (1.95 OR at 95% CI, 1.44–2.64) and low back pain (1.79 OR at 95% CI, 1.29–2.49). A positive correlation between physical activity levels, Verbal Descriptive Scale (VDS), and pain frequency have been observed for neck and low back pain (p-value < 0.05). Finally, low physical activity levels were associated with musculoskeletal pain onset and pain worsening.