Summary Periodic limb movements during sleep and obstructive sleep apnea are both associated with increased sympathetic tone, and have been proposed as risk factors for heart diseases and, in particular, cardiovascular disease. As sympathetic system activation may lead to dyslipidaemia, periodic limb movements during sleep could be an additional risk factor for cardiovascular disease in patients with obstructive sleep apnea. The aim of the study was to determine whether the presence of periodic limb movements during sleep affects serum lipid levels in obstructive sleep apnea. Total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, non‐ high‐density lipoprotein cholesterol and triglyceride levels were investigated in 4138 patients with obstructive sleep apnea in the European Sleep Apnea Database (ESADA) cohort, divided into those with periodic limb movements during sleep index ≥ 15 per hr ( n = 628) and controls ( n = 3510). ANCOVA adjusted for age, sex, body mass index, apnea–hypopnea index, alcohol intake, smoking status, diabetes, insomnia and study site was used to assess differences in lipids between periodic limb movements during sleep and controls. Patients with periodic limb movements during sleep (24% female, 54.4 ± 12.1 years, body mass index 31.9 ± 5.8 kg m −2 , apnea–hypopnea index 36.7 ± 25.4 per hr) had higher triglyceride (1.81 ± 1.04 versus 1.69 ± 0.90 mmol L −1 , p = 0.002) and lower high‐density lipoprotein cholesterol (1.19 ± 0.34 versus 1.24 ± 0.37 mmol L −1 , p = 0.002) levels, whilst there was no difference in either total cholesterol (4.98 ± 1.10 versus 4.94 ± 1.07 mmol L −1 ), low‐density lipoprotein cholesterol (3.04 ± 0.96 versus 2.98 ± 0.98 mmol L −1 ) or non‐ high‐density lipoprotein cholesterol (3.78 ± 1.10 versus 3.70 ± 1.05 mmol L −1 ) concentrations (all p > 0.05). The results remained unchanged after most sensitivity analyses. Patients with obstructive sleep apnea with periodic limb movements during sleep had more prevalent cardiovascular disease (11% versus 6%, p < 0.01). Periodic limb movements during sleep in obstructive sleep apnea is associated with dyslipidaemia independently of important confounders. Our results highlight periodic limb movements during sleep as an additional risk factor for cardiovascular disease in obstructive sleep apnea.