COVID-19 is a respiratory illness commonly associated with an inflammatory response that extends beyond lung symptoms and impairs blood clotting mechanisms. Hydroxysafflor yellow A, a key bioactive compound isolated from the florets of Carthamus tinctorius, is recognized as a potential therapeutic agent due to its combined anti-inflammatory and anticoagulant actions. Hence, this investigation assessed the influence of ethanol extract from C. tinctorius administered alongside dexamethasone on markers of coagulation in mice challenged with the SARS-CoV-2 spike protein. The florets of Carthamus tinctorius underwent extraction using 98% ethanol. The resulting concentrated extract was applied in the experiment. A total of twenty-five Balb/c mice were involved, with five serving as normal controls and twenty subjected to SARS-CoV-2 induction. These induced animals were then randomly allocated to seven-day regimens including vehicle only, dexamethasone at 2.5 mg/kg body weight, dexamethasone at 2.5 mg/kg body weight plus C. tinctorius extract at 400 mg/kg body weight, or dexamethasone at 2.5 mg/kg body weight plus C. tinctorius extract at 800 mg/kg body weight. Following treatment, analyses were conducted on the pulmonary tissues and blood samples from the mice. Induction with SARS-CoV-2 led to elevations across all evaluated coagulation parameters. Administration of dexamethasone singly or together with C. tinctorius extract at 400 mg/kg body weight produced no decreases in levels of D-dimer, plasminogen activator inhibitor-1, lactate dehydrogenase, platelet-to-leucocyte ratio, or neutrophil-to-leucocyte ratio. Conversely, the combination of dexamethasone and C. tinctorius extract at 800 mg/kg body weight restored normal values for D-dimer, PAI-1, and NLR in the SARS-CoV-2-challenged mice. Combining a higher dosage of C. tinctorius floret extract (800 mg/kg body weight) with dexamethasone provided advantages in alleviating coagulation disturbances linked to SARS-CoV-2..