The Centers for Disease Control and Prevention (CDC) said 25 more people had been affected since its last report on 16 May.
Two of the victims were from Minnesota, with the other three from Arkansas, California and New York.
It is the largest US outbreak of E. coli since 200 people fell ill in 2006.
According to the latest statement from the CDC, many of the people affected fell ill two to three weeks ago, when the contaminated lettuce was still on shop shelves.
Romaine lettuce from the Yuma growing region in Arizona is thought to be the source of the latest outbreak, although the Food and Drug Administration says no single grower, distributor or region can account for the spread.
The CDC said that some of the affected people had not eaten lettuce, but had contact with others who had fallen ill.
When eaten, it can cause diarrhoea, vomiting and even kidney failure in severe cases.
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