Ischemic stroke (IS) is emerging as an increasingly serious social issue with elusive etiology, few diagnostic markers, and limited treatment methods. Another concern in contemporary society is the prevalence of obesity, which is indicative of suboptimal well-being. Despite its association with established risk factors for stroke (such as hypertension and diabetes), several studies have reported a controversial phenomenon known as the "obesity paradox," whereby certain obese patients with stroke exhibited unexpectedly positive outcomes. In this study, a total of 68 plasma samples were collected including 36 controls and 32 IS patients, with further differentiation between obese and non-obese individuals in each group. A quantitative metabonomic approach based on H nuclear magnetic resonance (H NMR) was employed to identify differential metabolic markers of IS, and elucidate the impact of obesity on IS. The final results demonstrated that obesity did not have a significant impact on metabolites. It is important to note, however, that reliance on BMI as the sole indicator of obesity may be insufficient. Additional parameters, such as waist-to-hip ratio and waist circumference, should be considered. Furthermore, the impact of obesity on stroke is probably mediated through metabolic health, making it an intermediate factor rather than a direct cause. Additionally, the study identified approximately 30 metabolites exhibiting significant alterations in IS patients, with the primary metabolic pathways being energy metabolism, amino acid metabolism, lipid metabolism, and folic acid deficiency. These findings are significant for comprehending the potential mechanisms of IS and facilitating its rapid and early diagnosis for effective treatment.