Introduction Elevated body mass index (BMI) or overweight and obesity are pandemics. Lumbar disc herniation and sciatica occur in every population and present severe socioeconomic consequences. However, little is known regarding the role of BMI with lumbar disc herniation and sciatica. As such, the following large-scale study addressed the association of BMI, in particular overweight and obesity, with disc herniation, its global lumbar involvement and its implications with the development of sciatica. Materials and Methods A cross-sectional study of 2,596 Southern Chinese (mean age: 42 years; 60% females) was conducted assessing T2-weighted MRI, environmental and lifestyle factors, as well as clinical profiles of sciatica. On imaging, the presence of disc bulge/extrusion (DBE) and other spinal phenotypes from L1-S1 were assessed. Disc degeneration was assessed and graded based on the Schneiderman et al criteria and summated of all levels to produce a degenerative disc disease (DDD) score (potential score range: 0-15). A total DBE (TDBE) score of L1-S1 was calculated (potential score range: 0-10). Asian-modified BMI values and categories of underweight, normal weight, overweight, and obese were obtained for each subject. Results DBE was noted in 46.3% of the subjects, mainly occurring at L4-S1. The mean DDD and TDBE scores were 0.7 and 2.83, respectively. Historical prevalence of sciatica was 44.6%, with 17.9% reporting sciatica at the time of assessment. The mean BMI was 22.9 kg/m2 (7.2% underweight, 47.9% normal weight, 36.1% overweight, and 8.9% obese). Elevated DDD score was significantly correlated with an elevated TDBE score (r=0.610; p< 0.001). TDBE score significantly increased with elevated BMI categories ( p< 0.001). Multivariate analyses adjusting for covariates noted that elevated BMI was significantly associated with DBE (normal weight [Ref]; underweight OR: 0.71[95% CI: 0.49-1.03]; overweight OR: 1.26[95% CI: 1.04-1.52]; obese OR: 1.78[95% CI: 1.30-2.44]). TDBE score (OR: 1.36; 95% CI: 1.15-1.60) and obesity (OR: 1.68; 95% CI: 1.25-2.24) were significantly related with sciatica. Worse functional and disability scores were associated with sciatica ( p< 0.05). Conclusion Based on the largest population-based study to assess the role of BMI and its association with disc herniation, this study definitely noted that overweight and obesity significantly increased the likelihood of having lumbar disc herniation, its global severity, and the risk of developing sciatica. Disclosure of Interest None declared