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Three new species of the genus Senecio (Asteraceae, Senecioneae) belonging to S. ser. Suffruticosi subser. Caespitosi were discovered in the tributaries of the upper Tambo River, Moquegua Department, South Peru. Descriptions, diagnoses and discussions about their distribution, a table with the morphological similarities with other species of Senecio, a distribution map, conservation status assessments, and a key to the caespitose Peruvian species of S. subser. Caespitosi are provided. The new species are Senecio moqueguensis Montesinos, sp. nov. (Critically Endangered) which most closely resembles Senecio pucapampaensis Beltrán, Senecio sykorae Montesinos, sp. nov. (Critically Endangered) which most closely resembles Senecio gamolepis Cabrera, and Senecio tassaensis Montesinos, sp. nov. (Critically Endangered) which most closely resembles Senecio moqueguensis Montesinos.