New Mexico public health identified the first four cases of Salmonella Saintpaul infections associated with this outbreak. Soon after cases were identified in Texas and the Navajo Nation through PulseNet. Eventually cases in 43 states and Canada were identified.

In May, the first, multistate, case-control study initially implicated raw tomatoes. Salsa and guacamole, or other food items, were not significantly implicated. In June, increasing numbers of cases were reported from a growing number of states. Texas public health investigators investigated two clusters of illness associated with local Mexican-style restaurants. In these clusters, illness was associated with eating salsa (raw tomatoes and raw jalapeno peppers) and salsa (canned tomatoes and raw jalapeno peppers).

In late June, a second multistate case-control study significantly associated illness with eating pico de gallo, corn tortillas, and fresh salsa. Illness was not significantly associated with any other individual food items or ingredients. Beginning on June 30, a Minnesota cluster was analyzed by case control study. Illness was significantly associated with eating salsa, guacamole, red bell peppers, cilantro, and jalapeno peppers.

In early July, North Carolina investigated a cluster of 13 cases associated with a local Mexican-style restaurant. Illness was significantly associated with eating guacamole. The guacamole ingredients included avocado, raw Roma tomatoes, raw red onions, raw serrano peppers, cilantro, salt, and lime juice, but no jalapeno peppers. Between May and August, 33 restaurant associated clusters were investigated. Raw jalapeno peppers were not served in four of the restaurants. Serrano peppers were not served in 19 restaurants. Raw tomatoes were served by all restaurants. Of the four restaurants that did not serve jalapeno peppers, two had serrano peppers.

Also in July, a household-based, case control study was conducted in the Southwestern US. Having jalapeno peppers in the household in the week prior to illness onset was significantly associated with illness. Serrano peppers had a weak association with illness. During a traceback investigation, the FDA isolated the outbreak strain from a sample of serrano peppers and a sample of water from a holding pond from a farm in Mexico. In addition, Colorado Department of Health and Environment isolated the outbreak strain from a jalapeno pepper collected from a household of a case patient in Colorado who had purchased the peppers from Walmart. This pepper originated in Mexico, however the specific farm source could not be identified.