Background: The uncoupling proteins (UCPs) and β-adrenoceptors (ADRBs) are important for energy balance and may be involved in the pathogenesis of insulin resistance. Obesity is strongly hunted by insulin resistance and susceptibility genes for the two conditions could be separate or common. Variations within the UCPs and ADRBs genes may give important clues to their involvement in disease. Methods: A total of four single nucleotide polymorphisms (SNPs) in the genes UCP1, UCP2, UCP3, and ADRB1 were examined for association with obesity and insulin sensitivity (HOMA<sub>IR</sub>) in obese (n = 292) and healthy non-obese (n = 481) females. Results: None of the SNPs was associated with obesity status or body mass index. However, ADRB1 (rs1801253) was nominally associated with serum insulin (nominal p = 0.034) and HOMA<sub>IR</sub> (nominal p = 0.022). UCP3 (rs1800006) was in post-hoc analysis nominally associated with serum insulin and HOMA<sub>IR</sub> (nominal p = 0.013 and 0.048, respectively). UCP1 and UCP2 showed no association with insulin sensitivity. Conclusion: Polymorphisms in ADRB1 and UCP3 may contribute to insulin resistance rather than obesity among Swedish women.