AbstractObesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI). We assembled a cohort of women with BC (stage I–III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m²), overweight (25 ≤ BMI < 30 kg/m²), and obesity (BMI ≥ 30 kg/m²)). During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.19 mg/L) was associated with an increased risk of events (HR_adj:1.62 [95% CI = 1.14–2.28]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HR_adj:1.70 [95% CI = 1.09–2.66]; HR_adj:1.75 [95% CI = 1.08–2.86]), but in obesity, the estimate was less precise (HR_adj:1.73 [95% CI = 0.78–3.83]). For OS, high CRP was associated with increased risk of death (HR_adj:2.47 [95% CI = 1.62–3.76]). The association was strong in normal-weight and overweight (HR_adj:3.66 [95% CI = 1.95–6.87]; HR_adj:1.92 [95% CI = 1.06–3.46]), but less clear in obesity (HR_adj:1.40 [95% CI = 0.64–3.09]). To sum up, high CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.