The global impact of the SARS-CoV-2 infection has been substantial, affecting millions of people. Long COVID, characterized by persistent or recurrent symptoms after acute infection, has been reported in over 40% of patients. Risk factors include age and female gender, and various mechanisms, including chronic inflammation and viral persistence, have been implicated in long COVID's pathogenesis. However, there are scarce studies in which multiple inflammatory markers and viral load are analyzed simultaneously in acute infection to determine how they predict for long COVID at long-term follow-up. This study explores the association between long COVID and inflammatory markers, viral load, and lymphocyte subpopulation during acute infection in hospitalized patients to better understand the risk factors of this disease. This longitudinal retrospective study was conducted in patients hospitalized with COVID-19 in northern Mexico. Inflammatory parameters, viral load, and lymphocyte subpopulation during the acute infection phase were analyzed, and long COVID symptoms were followed up depending on severity and persistence (weekly or monthly) and assessed 1.5 years after the acute infection. This study analyzed 79 patients, among them, 41.8% presented long COVID symptoms, with fatigue being the most common (45.5%). Patients with long COVID had higher lymphocyte levels during hospitalization, and NK cell subpopulation levels were also associated with long COVID. ICU admission during acute COVID-19 was also linked to the development of long COVID symptoms.