Plasma levels of cocaine (COC) and two of its principle metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME) were determined by liquid chromatography–tandem mass spectrometry (LC/MS/MS) in samples collected up to 3 h after a subcutaneous injection of cocaine (10 mg/kg) on six different days between days 4 and 24 postpartum, a period of dramatic change in the endocrine state of the female rat. Locomotor activity was measured in the same animals during this period using automated animal activity monitors. Additional measures in males provide a link to existing literature. We found that plasma levels of cocaine and its metabolites, as well as their respective time courses, are remarkably uniform across the postpartum period in female rats, as are the effects of cocaine on locomotor activity. Data from males show accord with prior published values. COC and BE, but not EME levels, were higher in males, and the time courses of COC and BE levels after injection varied somewhat between postpartum females and males; however, neither baseline nor cocaine-induced locomotor activity differed between postpartum females and males. We conclude that in the postpartum rat, there are no significant differences in the peripheral processing or general accessibility of cocaine to the brain to activate motor systems across the postpartum period. These data are critical to our understanding of differences in the reward salience of cocaine across the postpartum period and in other adult rat models [Mattson BJ, Williams S, Rosenblatt JS, Morrell JI. Comparison of two positive reinforcing stimuli: pups and cocaine throughout the postpartum period. Behav Neurosci 2001;115:683–94, Mattson BJ, Williams SE, Rosenblatt JS, Morrell JI. Preferences for cocaine- or pup-associated chambers differentiate otherwise behaviorally identical postpartum maternal rats.