As well as gingival crevicular fluid (GCF), peri-implant sulcus fluid (PISF) may have a potential diagnostic value for the early identification of metabolic and destructive processes. The aim of this study was to analyze the potential impact of inflammation and loading on PISF myeloperoxidase (MPO) levels, in comparison with GCF. A total of 220 sites, dental implant (immediately [IL] or delayed loaded [DL]), and natural tooth, either healthy/noninflamed or gingivitis/inflamed, were classified. Clinical parameters were recorded, and GCF/PISF samples were obtained. GCF/PISF MPO levels were spectrophotometrically determined. Clinical parameters demonstrated increases with the presence of gingival/peri-implant inflammation. Total MPO levels were higher at inflamed tooth and implant sites compared to noninflamed/healthy sites (p < .05). Although they did not reach a significance level, inflamed IL sites had higher total MPO levels than inflamed DL sites (p = .401). Gingival index and total MPO levels exhibited significant correlations (p < .05). Using implants and natural teeth in the same study design, the findings of the present study support the close relationship between MPO production and inflammation, and may speculate a potential for loading of dental implants, contributing to the MPO content of PISF.