In the present study we investigated a possible causal link between circadian dysfunction and dopaminergic neurodegeneration in Drosophila using a toxin-induced model of dopaminergic neurodegeneration. We show for the first time that protocerebral anterior medial (PAM) neurons undergo selective neurodegeneration upon oxidative insults in a rhythmic fashion. Neuronal death in this cluster is exacerbated in per0 mutants, which is reversed by the rescue of per in clock neurons. Supporting this finding, we demonstrate the connectivity between clock neurons and PAM neurons using a trans-synaptic labeling technique. Furthermore, we find that a subgroup of PAM neurons, PAM-a1 subpopulation, is selectively and rhythmically vulnerable to oxidative insults. Using in vivo calcium imaging, we show that PAM-a1 neurons exhibit rhythms in calcium levels. Additionally, we demonstrate that toxin treatment causes changes in sleep but not activity levels in flies, implicating the degeneration of PAM-a1 neurons in deregulating non-motor functions.