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Herein we report the synthesis, antioxidant and neuroprotective power of homo-tris-nitrones (<b>HTN</b>) <b>1-3</b>, designed on the hypothesis that the incorporation of a third nitrone motif into our previously identified homo-bis-nitrone <b>6</b> (<b>HBN6</b>) would result in an improved and stronger neuroprotection. The neuroprotection of <b>HTNs 1-3</b>, measured against oligomycin A/rotenone, showed that <b>HTN2</b> was the best neuroprotective agent at a lower dose (EC₅₀ = 51.63 ± 4.32 μM), being similar in EC₅₀ and maximal activity to α-phenyl-<i>N</i>-<i>tert</i>-butylnitrone (<b>PBN</b>) and less potent than any of <b>HBNs 4-6</b>. The results of neuroprotection in an in vitro oxygen glucose deprivation model showed that <b>HTN2</b> was the most powerful (EC₅₀ = 87.57 ± 3.87 μM), at lower dose, but 50-fold higher than its analogous <b>HBN5</b>, and ≈1.7-fold less potent than <b>PBN</b>. <b>HTN3</b> had a very good antinecrotic (IC₅₀ = 3.47 ± 0.57 μM), antiapoptotic, and antioxidant (EC₅₀ = 6.77 ± 1.35 μM) profile, very similar to that of its analogous <b>HBN6</b>. In spite of these results, and still being attractive neuroprotective agents, <b>HTNs 2</b> and <b>3</b> do not have better neuroprotective properties than <b>HBN6</b>, but clearly exceed that of <b>PBN</b>.