Limited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy. The study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-II), and monocyte to HDL ratio (MHR) were calculated. HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C-reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742–0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases. Lipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia. •Lipid disbalance is present in COPD.•Lipid disbalance seems to occur later during the COPD progression.•Combined model of lipid and inflammatory parameters might identify COPD patients.