Faecal calprotectin (FCP) is a non-invasive biomarker of intestinal inflammation, levels of which are reported to be elevated in individuals with increased body mass index (BMI). We investigated whether weight loss (WL), induced by dietary and behavioural change in a community weight loss programme (Slimming World), was associated with a reduction in FCP in a longitudinal cohort study. We obtained paired stool samples at the start and 11-15 weeks into the weight loss programme in 40 individuals with a BMI >25kgm−2 and no known colorectal or systemic inflammatory condition. Eight of 40 (20%) ‘healthy’ participants had a baseline FCP greater than 50μgg−1 (the accepted adult cutoff value for FCP), termed FCPhigh. Although the degree (%) of WL was similar (5.1 FCPhigh versus 6.1 FCPnormal; P=0.63), only FCPhigh individuals, but not FCPnormal participants, demonstrated a reduction in FCP level (median 0.3-fold versus 1.0-fold (that is, no change) during the study period (P=0.065). A large prospective cohort study of FCPhigh and FCPnormal obese individuals is now required to determine the relationship between local mucosal inflammation and the systemic inflammatory state associated with obesity, as well as understand the relationship between FCP levels, WL and future risk of colorectal neoplasia.