Schizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Based on the latest concept of cognition, immunoinflammatory factors and structural magnetic resonance imaging (sMRI) features of the brain are considered markers of schizophrenia. This study explored the correlations between cognitive function and immunoinflammatory factors and sMRI in primary schizophrenia patients. Non-interventional cross-sectional study was conducted, including 21 patients with primary schizophrenia, who were identified based on the Diagnostic and Statistical Manual, Fifth Edition (DSM-V) and grouped under the observation group. Thirty healthy volunteers with age, gender, hand dominance, and education duration matched with those of the primary schizophrenia patients were recruited to the control group. All subjects underwent sMRI examination. MATRICS consensus cognitive battery (MCCB) was employed to assess the cognitive functions among patients with primary schizophrenia. The levels of serum amyloid A (SAA), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40) were measured by means of enzyme-linked immunosorbent assay (ELISA). Pearson's correlation analysis was carried out to analyze the correlation between immunoinflammatory factor levels and cognitive functions as well as brain sMRI features. The scores for all MCCB items and the total score for the observation group were apparently lower than those for the control group (p < 0.001), while the YKL-40 and SAA levels were notably higher in the observation group (t = 3.406, p < 0.05; t = 5.656, p < 0.001). Compared to the control group, the observation group exhibited reduced volumes of left and right insular lobes, left and right anterior cingulate cortexes, left and right hippocampi, right parahippocampal gyrus, right amygdala, left inferior occipital lobe, left superior temporal lobe, left temporal pole, and left middle and inferior temporal lobes (p < 0.001). The levels of YKL-40 and SAA were both negatively correlated with MCCB score (r = -0.3668, p = 0.004; r = -0.8495, p < 0.001). The volumes of right insular lobe, left and right anterior cingulate cortexes, right parahippocampal gyrus, right amygdala, and gray matter in left middle temporal lobe were all negatively correlated with the levels of YKL-40 and SAA (p < 0.05). Cognitive impairment in patients with primary schizophrenia is associated with increased serum SAA and YKL-40 levels and decreased gray matter volume.