Obese patients can significantly reduce weight and have a positive impact on obesity-related diseases. However, the risk of infection complications in obese people is higher than that in normal people, especially the surgical site infection. This research investigates the effect of antibiotics on weight change of obese patients after laparoscopic sleeve gastrectomy (LSG). A retrospective analysis was performed on 131 morbidly obese patients or obese patients with complications who received LSG treatment in the Third Hospital of Shanxi Medical University from 2013 to 2020. Patients were separated into the antibiotic group (59 cases) and the normal group (72 cases) according to whether antibiotics were used after surgery. The differences of postoperative weight-related indexes, inflammation-related indexes, and short-term complications were compared between the two groups. At 12-month follow-up, the % excess weight loss (%EWL) in the antibiotic group was statistically abated than that in the normal group ( 92.99 ± 28.60 , P < 0.01 ). In addition, the percentage of total weight loss (%total weight loss (%TWL)) was abated in the antibiotic group than in the normal group, but it was not significant ( P > 0.05 ). White blood cell count and neutrophil count in the antibiotic group were statistically raised than those in the in normal group ( P < 0.05 ), but neutrophil/lymphocyte ratio (NLR) showed no significant difference. Comparison of short-term postoperative complications between the two groups showed that the number of abdominal wall wound infection, body temperature > 38 ° C , and abdominal pain > 3 days in the antibiotic group were abated, but they were not statistically significant ( P > 0.05 ). Short-term antibiotic exposure after sleeve gastrectomy had an adverse effect on postoperative weight loss, with no significant improvement in short-term complications.