Background <p>Lupus retinopathy (LR) is a sight-threatening complication of systemic lupus erythematosus (SLE), yet disease-specific serologic biomarkers are lacking. Previous studies have shown that anti-recoverin (RCV) antibodies act as a biomarker of cancer-associated retinopathy and serum level of anti-RCV antibodies was elevated in SLE patients with fundus abnormalities. This study screened three candidate epitopes of RCV protein and evaluated anti-RCV epitope-specific autoantibodies as candidate serological markers for LR.</p> Methods <p>The epitopes of RCV protein were predicted by DNAStar software and cross-checked by BepiPred-2.0 and ABCpred. Serum autoantibodies against RCV and three linear epitopes (RCV^55–70, RCV^139–154, RCV^155–170) was determined by ELISA in SLE patients with LR (<i>n</i> = 48), without LR (non-LR, <i>n</i> = 48), and healthy controls (HC, <i>n</i> = 44). Statistical analyses included the Kruskal–Wallis with Dunn’s post-hoc tests, Mann-Whitney U test, Student’s t test, Chi-Square or Fisher’s exact tests, correlation analysis, logistic regression, and ROC analysis.</p> Results <p>Epitope-specific anti-RCV antibodies were significantly higher in LR than in non-LR SLE and HC (all <i>p</i> &lt; 0.05). Anti-RCV^139–154 demonstrated the highest diagnostic performance for identifying LR from SLE, with an AUC of 0.808 (95% CI: 0.721–0.895), a sensitivity of 54.2% and a specificity of 93.8%, outperforming full-length anti-RCV. Furthermore, anti-RCV^139–154 levels positively correlated with SLE disease activity (SLEDAI, <i>r</i> = 0.430, <i>p</i> &lt; 0.001), anti-dsDNA titers, and IgG levels, and inversely correlated with C3 and C4 levels (<i>p</i> &lt; 0.001). Notably, anti-RCV^139–154 levels were preferentially elevated in microvasculopathic LR and declined after treatment.</p> Conclusions <p>Epitope-specific anti-RCV antibodies, especially anti-RCV^139–154, may serve as novel biomarkers for early identification of LR in SLE patients.</p>