Objective <p>Olanzapine is an atypical antipsychotic drug which is effective in the treatment of schizophrenia (SCZ). Olanzapine exhibits significant pharmacokinetic variability and is associated with a higher propensity for metabolic abnormalities. Recent evidence indicates that the immune system may play a role in antipsychotic-induced metabolic abnormalities through antipsychotic-induced modifications of cytokine levels. This study examined the effect of age, sex, and BMI on serum olanzapine levels and their correlation with metabolic parameters and serum pro-inflammatory cytokine levels in SCZ patients.</p> Methods <p>A cohort of 104 SCZ patients receiving olanzapine treatment was recruited retrospectively for the investigation. Based on gender, age, and body mass index (BMI), the patients were divided into two groups each. Following a 4-week olanzapine treatment, the serum olanzapine concentrations and concentration/dose (C/D) ratios were compared between the two groups. The associations between the age, sex, and BMI with the serum olanzapine concentrations and C/D ratios were examined. Additionally, the relationship between the metabolic parameters and serum pro-inflammatory cytokine levels with the serum olanzapine concentrations and C/D ratios was analyzed.</p> Results <p>Female patients exhibited higher serum olanzapine concentrations (<i>t</i> = -3.523, <i>P</i> = 0.001) and C/D ratios (<i>t</i> = -2.816, <i>P</i> = 0.006) compared to male patients. Moreover, the gender exhibited a positive correlation with the serum olanzapine concentrations (<i>r</i> = 0.329, <i>P</i> = 0.001) and C/D ratios (<i>r</i> = 0.269, <i>P</i> = 0.006). The BMI exhibited a negative correlation with the serum olanzapine concentrations (<i>r</i> = -0.205, <i>P</i> = 0.037), but not the C/D ratios (<i>r</i> = -0.185, <i>P</i> = 0.060). Furthermore, no significant relationship was observed between the metabolic parameters with the serum olanzapine concentrations (<i>P</i> &gt; 0.05). Additionally, the serum olanzapine concentrations were negatively correlated with the serum IL-1β (<i>r</i> = -0.530, <i>P</i> &lt; 0.001), IL-6 (<i>r</i> = -0.446, <i>P</i> &lt; 0.001), and TNF-α (<i>r</i> = -0.464, <i>P</i> &lt; 0.001).</p> Conclusion <p>The patients’ gender and BMI might affect the serum olanzapine concentrations. The serum olanzapine concentrations were negatively correlated with the serum IL-1β, IL-6, and TNF-α levels, but not with metabolic parameters during a short-term use of olanzapine in Chinese patients with SCZ.</p>