<b><i>Background:</i></b> Serum urea level is a heritable trait, commonly used as a diagnostic marker for kidney function. Genome-wide association studies (GWAS) in East-Asian populations identified a number of genetic loci related to serum urea, however there is a paucity of data for European populations. <b><i>Methods:</i></b> We performed a two-stage meta-analysis of GWASs on serum urea in 13,312 participants, with independent replication in 7,379 participants of European ancestry. <b><i>Results:</i></b> We identified 6 genome-wide significant single nucleotide polymorphisms (SNPs) in or near 6 loci, of which 2 were novel (<i>POU2AF1</i> and <i>ADAMTS9-AS2</i>). Replication of East-Asian and Scottish data provided evidence for an additional 8 loci. SNPs tag regions previously associated with anthropometric traits, serum magnesium, and urinary albumin-to-creatinine ratio, as well as expression quantitative trait loci for genes preferentially expressed in kidney and gastro-intestinal tissues. <b><i>Conclusions:</i></b> Our findings provide insights into the genetic underpinnings of urea metabolism, with potential relevance to kidney function.