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SARS-CoV-2 can infect pets under natural conditions, which raises questions about the risk factors related to the susceptibility of these animals to infection. The status of pet infection by SARS-CoV-2 in Mexico is not well-understood. We aimed to estimate the frequency of positive household cats and dogs to viral RNA and antibodies for SARS-CoV-2 during the second wave of human infections in Mexico, and to recognize the major risk factors related to host and pet ownership behaviour. We evaluated two study groups, cats and dogs from COVID-19-infected/-suspected households (n = 44) and those admitted for veterinary care for any reason at several veterinary hospitals in Puebla City, Mexico (n = 91). Using RT-PCR, we identified the presence of SARS-CoV-2 RNA in swabs of four dogs (18.18%) and zero cats in COVID-19-infected/-suspected households; within this group, 31.82% of dogs and 27.27% of cats were tested IgG ELISA-positive; and neutralizing antibodies were detected in one dog (4.55%) and two cats (9.09%). In the random group (pets evaluated at private clinics and veterinary teaching hospital), 25.00% of dogs and 43.59% of cats were ELISA-positive and only one cat showed neutralizing antibodies (2.56%). Older than 4-year-old, other pets at home, and daily cleaning of pet dish, were each associated with an increase in SARS-CoV-2 infection (p < 0.05). Allowing face lick, sharing bed/food with pets and owner tested positive or suspected COVID-19 were not significant risk factors, but more than 4 h the owner spent away from home during the lockdown for COVID-19 (OR = 0.37, p = 0.01), and outdoor pet food tray (OR = 0.32, p = 0.01) significantly decreased the risks of SARS-CoV-2 infection in pets, suggesting that time the owner spends with their pet is an important risk factor., (© 2023 Wiley-VCH GmbH.)