Abstract Background High postpartum weight retention is a strong independent risk factor for lifetime obesity, cardiovascular disease, and type 2 diabetes in women. Interventions to promote postpartum weight loss have met with some success but have been limited by high attrition. Internet-based treatment has the potential to overcome this barrier and reduce postpartum weight retention, but no study has evaluated the effects of an internet-based program to prevent high postpartum weight retention in women. Methods/Design Fit Moms/Mamás Activas targets recruitment of 12 Women, Infants and Children (WIC) Supplemental Nutrition Program clinics with a total of 408 adult (>18 years), postpartum (<1 year) women with 14.5 kg or more weight retention or a body mass index of 25.0 kg/m2 or higher. Clinics are matched on size and randomly assigned within county to either a 12-month standard WIC intervention or to a 12-month WIC enhanced plus internet-based weight loss intervention. The intervention includes: monthly face-to-face group sessions; access to a website with weekly lessons, a web diary, instructional videos, and computer-tailored feedback; four weekly text messages; and brief reinforcement from WIC counselors. Participants are assessed at baseline, six months, and 12 months. The primary outcome is weight loss over six and 12 months; secondary outcomes include diet and physical activity behaviors, and psychosocial measures. Discussion Fit Moms/Mamás Activas is the first study to empirically examine the effects of an internet-based treatment program, coupled with monthly group contact at the WIC program, designed to prevent sustained postpartum weight retention in low-income women at high risk for weight gain, obesity, and related comorbidities. Trial registration This trial was registered with Clinicaltrials.gov (identifier: NCT01408147 ) on 29 July 2011.