Aetiological processes of polypoidal choroidal vasculopathy (PCV) remains poorly understood, but several studies indicate that immunity may play a role and report elevated levels of systemic C-reactive protein (CRP). In this systematic review and meta-analysis, we summarize available evidence in the field. We searched the databases PubMed/MEDLINE, EMBASE, Web of Science and the Cochrane Central on 19 March 2020. Two independent authors reviewed the studies and extracted data. Two independent authors reviewed the studies, extracted data and evaluated risk of bias within individual studies. Studies were reviewed in the text qualitatively and measures of association were included for quantitative analyses. Results from univariate analyses and multivariate-adjusted analyses were included for separate meta-analyses to evaluate whether the association was only due to factors associated with PCV. Four studies (246 patients with PCV and 2861 control individuals) were identified and included for a qualitative and quantitative analysis. Increased CRP was associated with PCV when pooling both univariate measures (OR 3.54, 95% CI: 2.13-5.89, p < 0.0001) and multivariate-adjusted measures (OR 3.05, 95% CI: 1.56-5.98, p = 0.0011). Sensitivity analyses confirmed robustness of the results. Increased CRP is associated to PCV, even after adjusting for demographics, lifestyle factors and co-morbidities. Clinical value of CRP in relation to PCV remains unclear, but the association gives much needed insight into the aetiology of a poorly understood disease.