Background: Hypocalcemia is highly prevalent in Coronavirus disease 2019 (COVID-19). There is limited evidence about the course and roles of different parameters in the occurrence of new or worsening hypocalcemia. Objectives: This prospective longitudinal study was conducted on hospitalized COVID-19 patients in Qazvin, Iran, in 2021. Methods: Serum levels of calcium, albumin, parathormone (PTH), 25(OH)D (vitamin D), magnesium, and phosphate were assessed on the first day (time one), as well as fourth to sixth days (time two) of hospitalization. Paired t-test, McNemar’s test, and multivariate logistic regression test were used to compare data at two times and evaluating the independent roles of different variables in the occurrence or worsening of hypocalcemia. Results: Out of a total of 123 participants, 102 patients completed the study. The mean serum calcium level significantly decreased from 8.32 ± 0.52 mg/dL to 8.02 ± 0.55 mg/dL at time two compared to time one (P < 0.001). Also, we witnessed new or worsening hypocalcemia at time two in 44 (55%) patients with normal serum calcium or mild hypocalcemia at time one (P < 0.001). The PTH level decreased from 42.17 ± 27.20 pg/mL to 31.28 ± 23.42 pg/mL (P < 0.001). The decrease in albumin and PTH levels was an independent significant factor in the occurrence or worsening of hypocalcemia at time two (OR = 1.27; 95% CI: 1.10 - 1.46; P = 0.001 for each 1 g/L decrement in albumin and OR = 1.29; 95% CI: 1.03 - 1.62; P = 0.026 for each 10 pg/mL decrement in PTH). Vitamin D deficiency or changes during hospitalization did not have a significant role in new or worsening hypocalcemia. Conclusions: Decreased PTH secretion and hypoalbuminemia have significant roles in the occurrence of new or worsening hypocalcemia during hospitalization due to COVID-19.