Objective: To investigate the correlation of serum high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), thyroid hormone levels with mental symptoms and cognitive function in patients with schizophrenia. Methods: A total of 75 patients with schizophrenia admitted to Third People’s Hospital of Fuyang City from March 2019 to December 2021 were selected as an observation group, and 50 patients with anxiety disorder were selected as a control group. The levels of hs-CRP, Hcy, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) were detected in the 2 groups. The correlation of the above serum inflammatory factors and thyroid hormone levels with the scores of Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MoCA) in schizophrenic patients was analyzed. Results: The levels of serum hs-CRP, Hcy in the observation group were significantly higher than those in the control group (both P<0.05), and the levels of T3, T4, and TSH were significantly lower than those in the control group (all P<0.05). There was no significant difference in FT3 and FT4 levels between the 2 groups (both P>0.05). Pearson correlation analysis showed that serum hs-CRP and Hcy were positively correlated with negative symptom scores of schizophrenic patients (both P<0.05). T3 and T4 levels were negatively correlated with negative symptom score (both P<0.05), TSH level was positively correlated with negative symptom score (P<0.05). Serum hs-CRP and Hcy levels were negatively correlated with MoCA score (r=−0.311, −3.256, both P<0.05). T3, T4, and TSH levels were positively correlated with MoCA score (r=0.363, 0.310, 0.326, all P<0.05). Conclusion: Schizophrenia patients have high hs-CRP, Hcy expression and abnormal thyroid hormone expression, and they are related to mental symptoms and cognitive impairment.