Abstract Background This study was conducted to explore the associations between serum albumin and markers of inflammation and cardiovascular disease in treated human immunodeficiency virus (HIV)-infected adults. Methods We conducted a nested study within in the SATURN-HIV trial in which 147 HIV+ adults on stable antiretroviral therapy were (1) virally suppressed, (2) had a low-density lipoprotein (LDL)-cholesterol level <130 mg/dL, and (3) were randomized to 10 mg daily rosuvastatin or placebo. Measures of serum albumin, carotid intima media thickness ([cIMT] surrogate marker of atherosclerosis), inflammation, T cells, monocyte activation, and gut integrity were assessed at baseline, 48 and 96 weeks later. Spearman correlations and linear mixed-effect models were used to assess associations with serum albumin. Results Mean age was 45 years, 80% of participants were male, and 69% were African American. Mean serum albumin was similar between the groups at all time points (4.01–4.09 g/dL in statin arm vs 4.02–4.11 g/dL in placebo arm; P = .08–0.35). Lower baseline serum albumin significantly predicted larger changes in cIMT, interleukin 6, D-dimer, tumor necrosis factor α receptor 1, fibrinogen, and high-sensitivity C-reactive protein (P ≤ .03) over 96 weeks independently of statin therapy. After adjusting for age, gender, smoking, body mass index, creatinine clearance, and LDL cholesterol, every 1 g/dL decrease in serum albumin at baseline remained associated with a 0.05-mm increase in cIMT over 96 weeks (P = .05). Conclusions Lower serum albumin in controlled HIV is associated with higher markers of chronic inflammation and hypercoagulation, which could explain the prior observation that serum albumin predicts nonacquired immune deficiency syndrome events in HIV. Serum albumin may predict progression of carotid atherosclerosis independent of traditional risk factors.