Changes in the ratio of the C-reactive protein (CRP) pentameric (anti-inflammatory) and (monomeric) isoforms during treatment of combined metabolic disorders with glucocorticoids are still poorly understood. The study aimed to assess plasma concentrations of CRP and its isoforms (pentameric and monomeric) in rats with obesity combined with arthrosis. The experiment involved 180 male Wistar rats (n = 180; 8–10 weeks, 200–250 g) randomized into five groups (n = 36). The first one represented the control; obesity and arthrosis were simulated in groups II–V. Groups I and II were administered 1.0 mL of saline; groups III–V were administered 1, 10, 100 ng/mL of dexamethasone daily for 10 days; concentrations of CRP and its isoforms (pentameric and monomeric) were assessed by ELISA on days 3, 5, and 10. Calculation was performed using the Statistica 10.0 software; the data were presented as M ± SD with 95% confidence intervals, with p < 0.05. The increase in CRP levels was reported in group (arthrosis + obesity): by 2.1% on day 3, 26.4% on day 5, 174.5% by day 10 (p < 0.001) relative to the control (group I). Dexamethasone 1 and 10 ng/mL reduced inflammation on day 3 (CRP levels decreased by 7.9% and 26.1%, respectively (p < 0.05)); CRP levels increased by 231.6% and 152.3% by day 10 (p < 0.001). The dose of 100 ng/mL reduced CRP levels by 9.5% on day 5, showing the increase by 149.0% on day 10; p < 0.001. In group II, the mCRP concentration increased by 287.1% by day 10, and in groups III, IV, and V it increased by 360.2%, 270.9%, and 280.6%, respectively (p < 0.001). The nCRP concentration decreased by day 10 in groups II and V (by 25.7% and 18.1%; p < 0.05). No deaths or adverse reactions were reported.  Conclusions: dexamethasone 1 and 10 ng/mL reduces the CRP concentration throughout 3 days, and the dose of 100 ng/mL up to 5 days with the development of resistance and the increase in total and monomeric CRP levels on day 10.