Objective - To determine whether functional alterations in neutrophils and mononuclear leukocytes are a consistent finding in dogs with inflammatory disease. Animals - 40 healthy dogs, 30 dogs with nonseptic inflammatory diseases, 25 dogs with septic inflammation, and 8 dogs with multiple organ dysfunction syndrome (MODS) secondary to sepsis. Procedures - Neutrophil size and granularity; expression of cell surface molecules including CD18, CD11b, and mature neutrophil antigen on neutrophils; and major histocompatability antigen class II (MHC class II) expression on monocytes and lymphocytes were evaluated by use of flow cytometry. Neutrophil size and granularity were evaluated by use of forward-angle versus side-angle light scatterplots. Leukocytes were labeled with monoclonal antibodies to quantify surface expression of leukocyte antigens. Results - Dogs with septic and nonseptic inflammatory diseases and MODS had an increase in percentage of neutrophils with increased size; dogs with septic inflammation and MODS had a greater percentage of neutrophils with decreased granularity. Dogs with septic and nonseptic inflammation and MODS had a low expression of CD18 and mature neutrophil antigen. Dogs with septic and nonseptic inflammation had an increase in CD11b expression. Monocytes from dogs with septic and nonseptic inflammation and MODS had a low expression of CD18. Monocytes and lymphocytes from dogs with septic and nonseptic inflammation and MODS had a low expression of MHC class II. Conclusions and Clinical Relevance - Neutrophils from dogs with septic and nonseptic inflammation circulate in an activated state, and some dogs have decreased MHC class II expression. Many dogs with MODS have a compensatory anti-inflammatory response that may compromise their responses to antimicrobials.