Background <p>Early life stress (ELS) is a risk factor for cardiovascular disease. Chronic low-grade inflammation has been linked to cardiovascular vulnerability. The interplay of ELS and inflammation in the context of coronary heart disease (CHD) remains elusive and was investigated in this prospective case control study.</p> Methods <p>In this prospective case-control study, <i>n</i> = 34 elective CHD inpatients at Heidelberg University Hospital were included between 2021 and 2023 and assessed regarding ELS by the Early Trauma Inventory Self Report Short Form (ETI-SR-SF). Salivary and venous blood samples were taken from the patients before and after a 6-minutes walking test. Median split of the population based on the ETI-SR-SF total score divided patients into a control group (&lt; 5 points, <i>n</i> = 19 patients, 42.11% female, age 68 ± 11.28 years) and an ELS group (≥ 5 points, <i>n</i> = 15 patients, 26.67% female, age 67 ± 9.74 years), which were analyzed accordingly.</p> Results <p>There were no differences in routine inflammatory parameters, including CRP (4.4 ± 4.6 vs. 8.8 ± 8.6&#xa0;mg/l), leukocytes (8.6 ± 3.2 vs. 7.4 ± 1.9 /nl) and procalcitonin (0.07 ± 0.04 vs. 0.07 ± 0.03 ng/ml) (Student’s T-test). Conversely, peripheral blood mononuclear cells (PBMCs) of ELS patients, showed significantly higher IL-1β mRNA expression upon walking compared to baseline (0.77 vs. 1.63-fold, <i>p</i> = 0.0459, Student’s T-test). Also, IL-6 release from ELS patient PBMCs was significantly increased at 24&#xa0;h (6.8 ± 7.1 vs. 53.5 ± 62.6 pg/ml, <i>p</i> = 0.0168, Student’s T-test). Ex-vivo exposure of PBMCs to high catecholamines blunted IL-6 release with upregulation of nuclear receptor 4A3 (NR4A3) expression in control vs. ELS patients (2.53- vs. 1.74-fold, <i>p</i> = 0.034, ANOVA).</p> Conclusions <p>Our results suggest a possible role of PBMCs in mediating inflammation in CHD patients with early childhood stress.</p>