Background further investigation is needed to define the long-term impact of pandemic lockdown in children. Objectives to examine changes in body mass index z-score (zBMI), lifestyle, Health-Related Quality of Life and proportion of overweight or obesity (OW/OB) in 6- to 9-year-old children in Argentina. Methods observational study with baseline measurements prior to lockdown and follow-up after eight months of strict restrictive measures (November 2020, first visit, n = 144) and after ten months of partial reopening (September 2021, second visit, n = 108). Anthropometric changes from baseline to first visit in lockdown group (LG) were compared with a historical control group (HCG, n = 134). Follow-up visits included anthropometric measures, lifestyle questionnaire and Pediatric Quality of Life Inventory. Results Change in zBMI was higher in LG [median, IQR: 0.46 (-0.00; 0.83)] vs HCG [median, IQR: 0.02 (-0.31; 0.27)]; p < 0.001, particularly in children with pre-existing OW/OB. In LG, zBMI was higher at first and second visit vs baseline (p < 0.001) and in second visit vs first visit for boys (p = 0.037) but not for girls. The proportion of children with OW/OB increased from baseline (43.5%) to first (56.5%) and second visit (58.3%) (p = 0.029). Unlike girls, the proportion of boys with OW/OB increased from baseline to first and second visit (p = 0.045). Change in zBMI was higher in children with less healthy habits (p < 0.001). Conclusions Weight gain was not reversed and continued to increase in boys when lockdown measurements were eased, although sedentary behaviors decreased and quality of life improved, indicating that the effects of pandemic lockdown are difficult to reverse.