Background: The presence of hyperreflective foci (HRF) in retinitis pigmentosa (RP) is a potentially new finding. We investigated the presence of HRF in SD-OCT images in eyes with RP and its relation to vascular, morphologic and metabolic findings in RP. Methods: The study was performed on 42 RP patients and 24 controls. Using SD-OCT, we calculated the amount of HRF within the entire retina (HRF-ER) and the outer nuclear layer (HRF-ONL). Retinal vessel diameters (μm) and oxygen saturation (%) values were measured using Oxymap T1. We evaluated the mean diameter in retinal arterioles (D-A) and venules (D-V), the corresponding oxygen saturation values (A-SO2, V-SO2) and the oxygen saturation difference (A-V SO2). Results: RP differed from controls by HRF-ER, HRF-ON and EZ-length (p < 0.001). D-A and D-V were narrower and A-SO2 and V-SO2 were higher in RP (p ≤ 0.001). Within RP, significant interactions were found between the HRF-ER* group and: BCVA, EZ length, D-A, A-SO2 and A-V SO2 (p ≤ 0.018). The HRF-ONL* group interactions were significant for: BCVA, EZ length, D-A, A-SO2 and A-V SO2 (p ≤ 0.014). Conclusion: The present study highlights the presence of HRF to reflect the vascular, morphologic and metabolic alterations in RP. These biomarkers seem to be associated with remodeling and apoptosis that occur with the progression of degeneration.