Intestinal mononuclear phagocytes (iMNP) are critically involved in mucosal immunity and tissue homeostasis. Two major non‐overlapping populations of iMNP have been identified in mice. CD103⁺ iMNP represent a migratory population capable of inducing tolerogenic responses, whereas CX3CR1⁺ iMNP are resident cells with disease‐promoting potential. CX3CR1⁺ iMNP can further be subdivided based on differential expression of CX3CR1. Using CX3CR1^GFP/+×RAG2^−/− mice, we demonstrate that CX3CR1^hi and CX3CR1^lo iMNP clearly differ with respect to their morphological and functional properties. Compared with CX3CR1^hi iMNP, CX3CR1^lo iMNP are polarised towards pro‐inflammatory responses already under homeostatic conditions. During a CD4⁺ T‐cell‐induced colitis, CX3CR1^lo cells accumulate in the inflamed mucosa and upregulate the expression of pro‐inflammatory cytokines and triggering receptor expressed on myeloid cells‐1 (TREM‐1). In contrast, CX3CR1^hi iMNP retain their non‐inflammatory profile even during intestinal inflammation. These findings identify two functionally distinct iMNP subsets based on differential expression of CX3CR1 and indicate an unanticipated stability of iMNP.