Long-term sustainable management of zebra chip (ZC) disease of potato requires development of tolerant or resistant germplasm. To this end, 283 potato varieties and breeding clones were infected with the ZC putative causal agent ‘Candidatus Liberibacter solanacearum’ (Lso) by potato psyllid vector inoculations in 2010, 2011, 2012, and 2013. Potato germplasm was then examined for development of fresh and fried ZC symptoms. Over multiple years 29 breeding clones exhibited little to no symptoms in freshly cut tuber slices, and five exhibited little to no symptoms in fried slices. These five presumed tolerant breeding clones were chosen for further screening to determine whether the lack of physiological responses to Lso infection was the cause of observed tolerance. To this end, tuber amino acid, sugar, and phenolic levels were compared between noninfected and Lso-infected plants. The five putative tolerant clones had less dramatic shifts in host physiology following Lso infection than the susceptible Atlantic cultivar. This suggested lack of host responses to Lso infection that result in major changes in tuber biochemistry is a potential mechanism of ZC resistance. However, the susceptible Atlantic cultivar did have consistently greater Lso titers compared with two of the tolerant entries, so for these reductions in Lso pathogen progression also might be a factor. Regardless, lack of host responses could still remain one trait that could be used to aid in selection of ZC-resistant potato varieties, as other tolerant lines had infection levels consistent with susceptible Atlantic cultivar. These results also suggest that germplasm derived from relatives of cultivated potato plants are viable sources of ZC disease resistance.