Varicella, a widespread disease of childhood, is usually benign but may in some instances lead to complications and eventually death. The aim of this study was to assess whether varicella severity in infants below one year of age was associated with the level of anti-varicella zoster virus (VZV) maternal antibodies. Two different data sets were used. Data on varicella-associated complications were collected through a national surveillance network involving 175 hospital-based pediatric wards. Data on levels of maternal acquired antibodies according to infants' age were extracted from a cohort of 345 full term infants enrolled in a prospective multicenter study in seven pediatric wards and/or pediatric emergency units. Among infants hospitalized for varicella complications, the overall prevalence of complications increased regularly from 10.4% in infants below 1 month of age to over 72.4% at 5 months of age. Conversely, the mean antibody titre decreased from 536 mIU/mL in the [0-1 [month group to below the 150 mIU/mL threshold at 3-4 months [Pearson coefficient = -0.956 (p < 0.001)]. Based on large numbers of infants, our results show for the first time, a strong inverse correlation between the levels of circulating anti-VZV maternal antibodies in full term infants and occurrence of varicella complications below one year of age. Infant protection could be optimized by increasing herd immunity, reducing the susceptibility of women in childbearing age and lowering the age of routine vaccination to 9 months. Additional vaccination for unprotected persons in close contact with infants below 12 months of age could be promoted.