Mayor Bill de Blasio announced the increase of cases of the evolving syndrome, possibly related to COVID-19, during a press conference Sunday morning.
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One death has been reported in the city and another nine cases are still pending investigation.
De Blasio said 47% of those 38 cases have tested positive for COVID-19 and 81% have antibodies.
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Symptoms of PMSIS include persistent fever, rash, abdominal pain and vomiting.
The mayor announced immediate actions were being taken to help fight the disease including testing all children with symptoms for antibodies, alerting parents of more than one million children and directing Regional Enrichment Centers to increase enforcement of masks and use of hand sanitizer.
In addition to the NYC cases, two other children have died in New York state, for a total of three fatalities.
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Gov. Andrew Cuomo said Sunday that another two deaths in the state are currently under investigation.
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Statewide, there are at least 85 cases -- mostly in children between the ages of toddlers and elementary school.
Health officials say they are still learning how the disease manifests. New York is helping develop national criteria for identifying and responding to the syndrome at the request of the Centers for Disease Control and Prevention, Cuomo said.
Children elsewhere in the U.S. have also been hospitalized with the condition, which was also seen in Europe.