Crohn's disease is a type of inflammatory bowel disease that leads to symptoms such as diarrhea, abdominal pain, weight loss, and increased risk of developing tumors. The immune system plays a vital role in the gastrointestinal tract by maintaining tolerance to commensal antigens and food. However, in Crohn's disease, this tolerance mechanism is disrupted, resulting in chronic inflammatory responses. The involvement of the immune system is central to Crohn's disease, with a wide range of immune cells including monocytes, being affected. Due to the limited understanding of the role of monocytes in Crohn's disease, our study aimed to clarify the cytokine production and activation profile of monocytes subsets in the context of this condition. We used multiparametric flow cytometry to analyze the status of monocyte, quantified gene expression using qPCR, and created a correlation matrix to connect the flow cytometry data with the qPCR results through a bioinformatics approach. Our findings indicate that patients with Crohn's disease show a reduction in all monocyte subsets. Additionally, classical monocytes exhibit an exhaustion profile characterized by increased CD38 expression and reduced IL-1β production following LPS stimulation in patient groups. These results suggest that monocyte subsets play distinct roles in the disease's pathophysiology of Crohn's disease, potentially contributing to chronic inflammation and impairing the resolution of the immune response.