We studied the photosensitised killing of retinal pigment epithelial (RPE) cells using two photosensitisers that localise in lysosomes. The ARPE-19 cell line was photosensitised using either acridine orange or cis-di(4-sulfonatophenyl)diphenylporphine. We then measured the amount of photoprotection provided to RPE cells by five synthetic carotenoid derivatives and by lutein. The synthetic carotenoid derivatives studied were the Girard's reagent P derivative (GRP) of retinal (GRP-retinal), the GRP derivative of β-apo-8′-carotenal (GRP-carotenal), the Girard's reagent T derivative of β-apo-8′-carotenal (GRT-carotenal), the GRP derivative of canthaxanthin ((GRP)2-canthaxanthin) and the dansyl hydrazine derivative of β-apo-8′-carotenal (dansyl-carotenal). We found that GRP-carotenal, GRT-carotenal (GRP)2-canthaxanthin and dansyl-carotenal were effective photoprotectors. All of these carotenoids had large singlet-oxygen quenching constants and had chemical structures designed to localise either in mitochondria or in lysosomes. In contrast, lutein and GRP-retinal were not effective photoprotectors. The failure of GRP-retinal to provide significant photoprotection may have been due to its relatively low singlet-oxygen quenching constant. Lutein is a potent singlet-oxygen quencher, but may not have provided significant photoprotection in this model because the lutein may have had a different subcellular distribution than the photosensitisers used.