Background: Coronavirus disease 19 (COVID-19), an infectious disease resulting from a virus known as severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), was discovered in China in 2019 and causes several mild to moderate respiratory conditions. This study aimed to reveal the changes in serum interleukin-10 (IL-10) and other parameters in Iraqi COVID-19 patients compared with healthy controls by studying the effects of enoxaparin and evaluating the potential of IL-10 as a disease activity marker. Methods: This was a case–control study that included 180 samples: 90 patients hospitalized with COVID-19 from November 2022 to 20 April 2023 (40 patients had never used enoxaparin, whereas 50 patients had taken enoxaparin) and 90 healthy, age- and sex-matched control. There were 44 female patients and 46 male patients. The mean age of the patients and controls was 53.8 years vs. 50.8 years, respectively. The sandwich enzyme-linked immunosorbent assay (ELISA) method was used to measure IL-10 levels, while other parameters were assessed using the colorimetric method. Results: The results of the study indicated highly significant changes between the patients and healthy controls in IL-10, D-dimer, and C-reactive protein (CRP) levels, as well as liver and renal functions. These findings elucidated a significant change between enoxaparin patients and non-enoxaparin patients in IL-10, D-dimer, and CRP levels. However, the liver and renal functions were not significantly altered. The Spearman’s rank correlation test investigated the relationship between serum IL-10 and CRP. Conclusions: The results displayed a strong positive relationship between IL-10 and CRP. There were no significant differences between the other analyzed parameters; consequently, the patients had higher concentrations of IL-10, D-dimer, and some other parameters than the healthy controls. Additionally, IL-10 may be used as a marker of disease activity. Enoxaparin will likely help control IL-10 and D-dimer concentrations in patients since IL-10 levels decreased in patients treated with enoxaparin.