Tomato fruit growth is characterized by the occurrence of numerous rounds of DNA endo-reduplication in connection with cell expansion and final fruit size determination. Endo-reduplication is an impairment of mitosis that originates from the selective degradation of M phase-specific cyclins via the ubiquitin-mediated proteolytic pathway, requiring the E3 ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). Two types of APC/C activators, namely CCS52 and CDC20 proteins, exist in plants. We report here the molecular characterization of such APC/C activators during fruit development, and provide an in planta functional analysis of SlCCS52A, a gene that is specifically associated with endo-reduplication in tomato. Altering SlCCS52A expression in either a negative or positive manner had an impact on the extent of endo-reduplication in fruit, and fruit size was reduced in both cases. In SlCCS52A over-expressing fruits, endo-reduplication was initially delayed, accounting for the altered final fruit size, but resumed and was even enhanced at 15 days post anthesis (dpa), leading to fruit growth recovery. This induction of growth mediated by endo-reduplication had a considerable impact on nitrogen metabolism in developing fruits. Our data contribute to unravelling of the physiological role of endo-reduplication in growth induction during tomato fruit development.