Obesity is a chronic inflammatory condition, and elevated white blood cell counts (WBC) have widely recognized associations with inflammatory conditions. The authors explored the relationship between the WBC and degree of obesity, basic anthropometry, and clinical and biochemical markers of the metabolic syndrome at baseline, and with weight loss following Lap-Band^® surgery. 477 patients with complete biochemical and clinical data at baseline and at 2 years were selected for analysis. Paired analysis assessed the change in WBC at 2 years, and stepwise linear regression assessed factors independently associated with baseline counts and any change at 2 years. Mean ± SD weight loss at 2 years was 29.3 ± 16.2 kg. There were significant decreases in total WBC (−12.2%), and major components, neutrophils (11.7%) and lymphocytes (6.9%), at 2 years (P<0.001 for all). Baseline WBC, neutrophils and lymphocyte counts increased with increasing BMI and decreased with age. Insulin levels were independently positively associated with higher neutrophil counts and triglycerides with higher lymphocyte counts. Age, gender, BMI and components of the metabolic syndrome when modeled together accounted for <10% of the variance of baseline counts. Higher BMI predicted a greater fall in the neutrophil counts at 2 years. Change in BMI at 2 years was the only independent predictor of the change in both neutrophils and lymphocytes, but accounted for <10% of the variance of change. BMI contributes to both baseline and weight loss WBC. However, crude WBC counts are influenced in minor ways by obesity markers and have limited value as clinical markers.