Obesity is a common comorbidity of asthma and is associated with more severe disease, which is more difficult to treat and does not respond well to existing asthma therapies. (1, 2) People living with obesity are more likely to consume a high-fat diet, which contains a large amount of saturated and omega-6 fatty acids. (3, 4) A high consumption of omega-6 fatty acids leads to an increased production of eicosanoids, such as prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), which have pro-inflammatory effects. (4, 5) This study aims to determine whether prostaglandins and leukotrienes are differentially expressed in adults with asthma and obesity compared to those with asthma but without obesity, and to investigate whether this difference is correlated with systemic inflammation and asthma severity as measured by lung function. Participants were adults with stable physician-diagnosed asthma aged 18-55 years, with (n = 34) and without (n = 67) obesity. Obesity was defined as a body mass index (BMI) ≥30kg/m2. Plasma PGE2 and LTB4 concentrations were measured using high-sensitivity ELISA (Thermo Fisher Scientific and Cayman Chemical). Compared to participants without obesity, those with obesity had significantly lower mean (SD) %predicted forced vital capacity [FVC%; 95.7(11.6) vs 89.4 (11.3), p = 0.013] and higher median (IQR) systemic inflammation as measured by plasma interleukin (IL)-6 [1.02 (0.79, 1.26) vs 1.72 (1.45, 2.23) pg/mL, p < 0.001]. Although median (IQR) PGE₂ and LTB₄ concentrations did not significantly differ between participants without versus with obesity [PGE₂: 1404 (1017, 1810) vs 1472 (1209, 1942) pg/mL, p = 0.517; LTB₄: 68.4 (50.8, 84.1) vs 79.8 (63.2, 85.2) pg/mL, p = 0.058], LTB₄ was positively correlated with plasma IL-6 (rs = 0.433, p < 0.001) and sputum macrophage count (rs = 0.290, p = 0.007), while PGE₂ was inversely correlated with sputum IL-6 (rs = –0.213, p = 0.047). These findings suggest that obesity in asthma is characterised by increased systemic inflammation and reduced lung function, while PGE₂ and LTB₄ may differentially associate with systemic and airway inflammatory markers. Future studies should explore whether dietary manipulation of omega-6 and omega-3 fatty acid concentrations modulates eicosanoid concentrations and airway and systemic inflammation in people with asthma.