Purpose During the COVID-19 quarantine period, most outdoor activities and events were banned, resulting in a decrease in physical activity (PA) and prolonged sitting (PS) time, which are significant factors in the development of lower back pain (LBP). The aim of this study was to evaluate the association between physical inactivity and daily sitting time during quarantine with LBP among the Saudi Arabian population. Patients and Methods In this cross-sectional study conducted at King Abdulaziz University Hospital, 288 participants were recruited using an online, self-administered questionnaire in Arabic. It consisted of 21 questions assessing back pain, PA, and daily sitting time before and during quarantine. The main outcome measures included demographics, low back pain levels, daily sitting time, and PA level. Results The participants consisted of 236 women and 52 men aged 18–65 years. During quarantine, 74% of participants sat most of the time and did not exercise or performed less exercise. Furthermore, almost half of the participants did not engage in PA both before and during the quarantine. There was an increase in the prevalence of LBP, with only 44.8% of participants presenting with LBP before quarantine and 59.4% having it during quarantine. A statistically significant association was found between daily sitting time and LBP (P=0.007) and PA and LBP (P=0.045) during quarantine. However, there was no significant association between age and painkiller use for LBP (P=0.251). Conclusion Our study highlights the relationship of physical inactivity and PS during quarantine with an increase in the prevalence and intensity of LBP. The limitations of the study include the use of self-reports, a small sample size, and unequal survey distribution. A well-distributed survey with a larger sample size is necessary to obtain an adequate representation of the entire Saudi population.