Minimal information is available on treatment strategies with anti-inflammatory drugs in systemic inflammation of birds. The present study was conducted to evaluate the comparative effects of meloxicam and dexamethasone at different single doses on clinical outcome and cardiovascular parameters in broilers with experimental systemic inflammation induced by E. coli lipopolysaccharide)LPS(. A total of 36 Ross broiler chickens were divided to six groups (n = 6 males/group): (NC) negative control; (PC) positive control: LPS (from Escherichia coli O55:B5, 0.5 mg/kg, intravenously); (T1) LPS + meloxicam (0.5 mg/kg; intramuscular (IM)); (T2) LPS + meloxicam (2 mg/kg, IM); (T3) LPS + dexamethasone (2 mg/kg, IM); and (T4) LPS + dexamethasone (4 mg/kg, IM). Anti-inflammatory drugs were administered right after the induction of endotoxemia. LPS significantly influenced clinical signs' severity scores and increased nitric oxide (NO) and cardiac troponin I (cTnI) levels and creatine kinase-MB (CK-MB) activity in the PC group. A biphasic response of body temperature was observed in LPS-induced birds. Administration of both drugs in low or high dose improved the therapeutic outcome as shown by reduced clinical signs' severity scores in treatment groups. The higher dose of dexamethasone was more effective in hypothermic phases. Meloxicam or dexamethasone induced a decrease in serum CK-MB activity and cTnI level, whereas no change was observed in serum NO levels and aspartate aminotransferase (AST) activity. In conclusion, a single administration of meloxicam or dexamethasone was effective in the acute management of a systemic inflammatory process in chickens. Considering both effects and plausible side effects, dexamethasone at 2 mg/kg appears to be preferable in terms of therapeutic effects.