The relationship between excessive nutrient intake and hepatic endoplasmic reticulum stress (ER stress) is well stablished. However, mechanisms underlying the progression from adaptive to apoptotic pattern are still unclear. This study sought to investigate the effects of high‐sucrose diet on metabolic disorders associated to hepatic ER stress. Weaned Swiss mice received standard chow (CTR) or high‐sucrose diet (HSD; 25% sucrose) for distinct periods of 30 (CTR30 and HSD30) and 60 (CTR60 and HSD60) days. Weight gain, food intake, feed efficiency and Lee index (LI) were measured for obesity development assessment. At each treatment end, glucose (GTT) and insulin (ITT) tolerance tests were performed. Blood, white adipose tissue (WAT) depots and liver were collected upon euthanasia of anesthetized animals. Serum glucose (GL), triglycerides (TG), total cholesterol (TC) and free fatty acids (FFA) levels were determined. WAT depots were weighed and their lipolytic activity assessed. Hepatic tissue was used to determine the lipid profile and gene expression of ER stress (ATF6, IRE1α, PERK, GRP78, PDI, NRF2) and pro‐apoptotic (CHOP and caspase 2) markers. Only HSD60 showed higher weight gain (8%), LI (3%) and feed efficiency (31%), as compared to CTR60. WAT was 2‐fold higher in HSD60 than in HSD30, whereas both of them were significantly higher than their controls. Lipolytic activity under isoproterenol‐stimulation was 40% lower in HSD60. Serum GL and TC were increased in 20 and 40%, respectively, in both HSD groups. However, TG (43%) and FFA (25%) were increased only in HSD60. Area under the curve of GTT was augmented in both HSD30 (14%) and HSD60 (41%), as compared to their controls. Whereas only HSD60 presented reduced kITT (37%) and increase TyG (8%). Total fat liver content was increased in 22 and 61% for HSD30 and HSD60, respectively. On the other hand, hepatic TG was augmented only in HSD60 (69%). HSD30 presented increased hepatic gene expression of GRP78 (57%), PERK (83%), IRE1α (49%), ATF6 (70%), PDI (41%) and NRF2 (32%), and reduced expression of CHOP (39%). An opposite pattern was found in HSD60, with reduced expression of PERK (34%), IRE1α (52%), ATF6 (36%) and PDI (46%), and increase expression of CHOP (72%). Notwithstanding, caspase‐2 expression did not change in any group. Therefore, our data suggest the HSD intake for up to 60 days after weaning rapidly promotes metabolic disorders associate to early onset of hepatic ER stress, which promptly progress from an adaptive to a pro‐apoptotic pattern.Support or Funding InformationFAPEMA, CNPq, CAPES and UFMA.