Objective. It has been reported that the prevalence of metabolic syndrome (MS) in multiepisode patients with schizophrenia is 35.3%, which is 2- to 4-fold higher than in the general population. The study is designed to compare the glycolipid metabolism in patients with first-episode schizophrenia (FES) with sex- and age-matched healthy controls to investigate changes in serum levels of homocysteine (Hcy), macrophage migration inhibitory factor (MIF), and high-sensitive C-reactive protein (hs-CRP) and their relationships with the glycolipid metabolism in patients with FES. Methods. His case-control study included 88 patients diagnosed with FES and 88 sex- and age-matched healthy controls. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), and 17-item Hamilton Rating Scale for Depression (HAMD-17). Patients with FES were classified into MS and non-MS groups. Results. There were significant differences in the education level, body mass index (BMI), and waist circumference between the patients with FES and healthy controls (all
p
>
0.05
). The patients with FES had higher levels of FPG and blood glucose at the oral glucose tolerance test (OGTT) (2 h glucose) concomitant with higher proportion of impaired glucose tolerance (IGT) and homeostasis model assessment of insulin resistance (HOMA2-IR) than healthy controls (all
p
<
0.001
). It was revealed that the patients with FES showed higher serum levels of Hcy, MIF, and hs-CRP than healthy controls (all
p
<
0.001
). The serum level of Hcy shared positive correlations with the score of PANSS totals (r = 0.551) and the negative syndrome of the PANSS scale (r = 0.494). The serum levels of MIF and hs-CRP was only positively correlated with the negative syndrome of the PANSS scale (r = 0.320 and r = 0.446). The level of Hcy shared positive correlations with the levels of FPG, 2 h glucose, and HOMA2-IR; the level of MIF was only positively correlated with the level of HOMA2-IR; the level of hs-CRP had a positive correlation with both levels of FPG and 2 h glucose (all
p
<
0.001
). The levels of Hcy, MIF, and hs-CRP all shared positive correlations with the TG level and negative correlations with the HDL-C level (all
p
<
0.001
). There were remarkable differences between the MS and non-MS groups with regard to BMI, waist circumference, negative subscale of the PANSS scale, FPG, TG, and HDL-C (all
p
<
0.05
). Elevated levels of Hcy, MIF, and hs-CRP were detected in the MS group compared to the non-MS group (all
p
<
0.05
). Conclusion. These findings suggest that increased concentrations of HCY, MIF, and hs-CRP may contribute to the abnormal glycolipid metabolism in the context of schizophrenia.