To better understand the physiological basis of obesity in women, we investigated whether obesity or menstrual-cycle phase affects laboratory-test-meal size or meal-stimulated plasma cholecystokinin (CCK) concentration. Women with healthy weight (BMI 18.5–24.9 kg/m2, N = 16) or obesity (BMI 30-39.9 kg/m2, N = 20) were tested once in the late-follicular or peri-ovulatory phase (LFPO) and once in the mid-luteal phase (ML). Meals of ham sandwiches were offered and blood was sampled. Menstrual-cycle phases were verified with participants’ reports of menses and measurements of progesterone and LH concentrations. Women with obesity ate significantly larger meals than women with healthy weight; 711 [402-1013] kJ (mean, 95%CI), P = 0.001, during the LFPO and 426 [105-734] kJ, P = 0.027, larger during the ML. Women with healthy weight ate smaller meals during LFPO than ML (decrease, 510 [192-821 kJ], P = 0.008), but women with obesity did not (decrease, 226 [-87-542] kJ, P = 0.15). CCK concentrations 18-30 min after meal onset were less in women with obesity than in women with healthy weight during LFPO (3.6 [3.1–4.1] versus 6.1 [4.5–7.7] pMol/L; P = 0.004), but not during ML; with a significant interaction effect, 1.8 [1.2-2.4] pMol/L, P = 0.048. Women with obesity consumed larger meals than women with healthy weight but displayed reduced meal-stimulated plasma CCK concentrations. These data are consistent with the hypothesis that a defect in CCK secretion compromises satiation in obese women and contributes to the development or maintenance of obesity.