Background: We evaluated the association between white adipose tissue parameters before bariatric surgery (BS) and post-surgical weight loss, with an especial focus on extracellular matrix (ECM) gene expression. Methods: Paired samples from subcutaneous (SAT) and visceral adipose tissue (VAT) were obtained from 144 subjects undergoing BS. The association between total body weight loss (%TBWL) at 12 months after BS and the histological characteristics and gene expression of selected genes in SAT and VAT was analyzed. Results: Fat cell area, size-frequency distribution, and fibrosis in SAT or VAT prior to surgery were not associated with %TBWL. On the contrary, the SAT expression ofCOL5A1andCOL6A3was associated with %TBWL after BS (bothp< 0.001), even after adjusting for age, gender, baseline BMI, and type 2 diabetes status (T2D). Furthermore, in logistic regression analyses, the expression of these genes was significantly associated with insufficient WL (IWL = TBWL < 20%) after BS (respectively,p= 0.030 andp= 0.031). Indeed, in ROC analysis, the prediction of IWL based on sex, age, BMI, T2D, and the type of surgery (AUC = 0.71) was significantly improved with the addition of SAT-COL5A1gene expression (AUC = 0.88, Z = 2.13,p= 0.032). Conclusions: Our data suggest that the expression of SAT ECM-related genes may help explain the variability in TBWL following BS.