<p>Obesity is a risk factor for chronic diseases and early death; however, the underlying mechanisms are not fully understood. Whereas insulin resistance and inflammation are established pathways in several of these relationships, it is less clear how increases in body adipose tissue relate to these pathways and disease risk. Several adipose tissue-derived blood-based biomarkers have been identified as purported mediators, including adipokines, inflammatory cytokines and sex steroid hormones. Traditionally, these markers were discovered in animal models and their relevance in humans has then been investigated in epidemiological studies. Today, proteomics and metabolomics approaches in human observational studies are used to discover obesity biomarkers in blood, supported by Mendelian randomization studies to draw causal inferences. Here we review adipose tissue-derived blood-based obesity biomarkers and their relevance for disease risk, along with their potential role as mediators. Proteomics and metabolomics studies have partly re-identified traditional biomarkers, but more large-scale prospective analyses are needed to obtain evidence of the relevance of omics-based and traditional obesity biomarkers to disease.</p>