We report the preparation of chiral oxygen atom‐appended porphyrazines (pzs) as biomedical optical agents that absorb and emit in the near‐IR wavelength range. These pzs take the form M[pz(A4‐nBn)], where “A” and “B” represent moieties appended to the pz’s pyrrole entities, A = (2R,3R) 2,3‐dimethyl‐2,3‐dimethoxy‐1,4‐diox‐2‐ene, B = β,β′‐di‐isopropoxybenzo, M is the incorporated metal ion (M = H2, Zn), and n = 0, 1, 2 (‐cis/‐trans) and 3 (). When dissolved in polar media, H2[pz(trans‐A2B2)] 5a does not fluoresce and has a negligible quantum yield for singlet oxygen generation (ФΔ = 0.074 ± 0.001, methanol), as measured by the photo‐oxidation of DMA. However, when sequestered in the nonpolar environment of a liposome, it displays strong NIR emission (λmax = 705 nm, Фf = 0.087) and an extremely high singlet oxygen quantum yield (ФΔ→1). Of this series, H2[pz(trans‐A2B2)] 5a is attractive as a potential optical probe, showing strongly fluorescent uptake by cells in culture, while 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide measurements of cell viability show no evidence of dark toxicity. This agent does show significant photoinduced toxicity suggesting that pzs such as 5a have promise as “theranostic” optical agents that can be visualized with fluorescence imaging while acting as a sensitizer for photodynamic therapy.