Background Despite the wide variety of Covid‐19 symptoms, pain and the related mechanisms underlying unsettled nociceptive status are still under‐prioritized. Understanding the complex network of Covid‐19‐related pain may result in new lines of study. It is unknown whether patient's immunological background influences pain in the acute phase of Covid‐19, including musculoskeletal pain. Thus, we evaluated the blood levels of selected molecules that are upregulated in SARS‐CoV‐2 infection and analyzed a possible correlation with pain during Covid‐19. Methods A cohort of 20 hospitalized patients with confirmed diagnoses for Covid‐19 were evaluated in the context of pain. Visual analogic scale (VAS) was applied to quantitate pain level. Blood tests were used to determine the systemic levels of cytokines (IL‐10 and IL‐1β), substance P, and leptin. The data were correlated when appropriate to determine the association between pain‐related markers and assessed pain intensity. Results Our findings show that systemic levels of IL‐10 have strong negative correlation with pain intensity on Covid‐19 patients. Additionally, we also show that leptin systemic levels were increased in Covid‐19 patients with pain, however, with moderate positive correlation between these events. IL‐1β and SP levels did not differ between Covid‐19 patients with or without pain. Men reported less pain compared to women. No differences were found between genders in the levels of the molecules evaluated in patients with pain. Conclusion IL‐10 has been described over the years as an anti‐inflammatory and analgesic cytokine. The present data support that low IL‐10 levels might contribute to Covid‐19‐associated pain.