Lipoprotein apheresis (LA) is used for severe dyslipidemia but can remove non-lipid plasma constituents. In this systematic review and meta-analysis, we synthesized evidence on LA-associated changes in albumin, total protein (TP), and α2-macroglobulin (α2M). PubMed, Scopus, and Web of Science were searched from inception to August 2025 for human observational studies reporting pre-/post-apheresis values for albumin, TP, or α2M. Pooled effects were summarized as weighted mean differences (WMD) with 95% CIs. Prespecified subgroup analyses included apheresis duration (≥ 1 year vs. < 1 year), disease background, and apheresis method. Twenty-eight publications met eligibility (albumin: 22 publications/39 studies; TP: 21 publications/34 studies; α2M: 6 publications/7 studies). LA was associated with lower post-procedure levels of albumin (WMD = -3.80 g/L; 95% CI: -4.61 to -2.99; p < 0.001), TP (WMD = -8.73 g/L; 95% CI: -11.06 to -6.41; p < 0.001), and α2M (WMD = -65.79 mg/dL; 95% CI: -88.98 to -42.60; p < 0.001). Reductions were observed across durations (< 1 year and ≥ 1 year), disease groups, and apheresis methods, with larger albumin decreases in DALI-based protocols and smaller in other methods. Between-study heterogeneity was high but diminished in several subgroups; meta-regression suggested background disease as a potential contributor. Across observational studies, LA reduced albumin, TP, and α2M immediately post-procedure. Magnitudes vary by method, clinical context, and treatment duration. These findings support routine monitoring of protein profiles during maintenance LA.