In August 2022 local, state and federal public health agencies reported an outbreak of E. coli O157:H7 infections linked to sandwiches sold at Wendy's restaurants in six states. The suspected source was romaine lettuce served on sandwiches. However, Wendy's meals eaten by sick people had many similar ingredients and no laboratory or traceback data confirmed romaine lettuce as the source. A total of 109 people infected with the outbreak strain of E. coli O157:H7 were reported from 6 states. Illnesses started on dates ranging from July 26, 2022 to August 17, 2022. Fifty-two people were hospitalized and 13 developed hemolytic uremic syndrome ((HUS).

State and local public health officials interviewed people about the foods they ate in the week before they got sick. Among 92 people with detailed food history, 68 (83%) reported eating at a Wendy's restaurant in the week before their illness started. The Wendy's restaurants where sick people ate were located in Indiana, Kentucky, Michigan, New Jersey, Ohio and Pennsylvania.

Several food items were tested during the outbreak investigation, but the outbreak strain was not identified.

On October 4, 2022 the outbreak was declared over.