Bacterial persistence, found in dormant and starved cells, is a health threat due to transient antibiotic tolerance. Harnessing a novel method for persister generation, we determined the proteome, metabolite levels and the physiology of E.coli persisters in and during entry into dormancy and starvation. In contrast to starved persisters, dormant persisters present in nutrient-rich conditions produced energy and grew, while both types had extremely low metabolite pools. The proteome of dormant cells governed by starvation response reached a unique state characterized by diminished anabolism, stress response and preservation of central metabolism protein levels. While starved cells approaches the same proteome, the limited carbon and energy source did not allow them to reach it, which caused their higher sensitivity to certain antibiotics. We present a conceptual model in which depleted metabolite pools resulting from initial persistence triggers provide a primitive, feed-forward starvation signal that sustains the growing persistent phenotype.