Background: Coronaviruses are large groups of viruses that cause illness in humans and animals. This virus has a higher degree of lethality than other endemic viruses Covid-19 diagnosis is based on viral detection, isolation, or serological changes. For cytopathic effects, sputum cytology is routinely performed for nearly all patients with chest symptoms. Objective: The study aimed to find Cytological change in sputum samples of COVID -19 patients in Shendi town. Materials and Methods: This study includes 45 subjects. Thirty were known as Covid 19 positive cases by PCR, and 15 were healthy subjects. Two sputum smears were collected from the study group then fixed in (95% Ethanol alcohol) and stained with Papanicolaou and Giemsa stains, then screening for any cytomorphological changes and microbes. Result: In cytology screening, intranuclear inclusion and inflammatory cells were observed in all sputum samples (100%) of patients infected with covid-19, other cytomorphological changes that appeared were nuclear atypia (96.6%), cytolysis (64.4%) and destructive change (fibrocytes) in (30%). None of the cytomorphological changes mentioned above were observed in the control sample. Co-infection with bacteria and fungi (aspergillus & Candida) exists in (66.6%) of Covid-19 patients. There was a statistically significant correlation between infection with covid-19 and the cytomorphological changes characterized in their sputum P. value was less than (0.05). Intranuclear inclusion in this study was a specific and sensitive indicator for Covid-19. There was no correlation between the period of infection and distractive change appearance or invasion with micro-organisms of the study group (P. value more than 0.05), But confections with microorganisms were statistically correlated to the age of the study group (P. value less than 0.05). Conclusion: Cellular changes and consistency of Sputum and saliva samples can provide inexpensive, rapid diagnostic, minimally invasive techniques for Covid-19, particularly in densely populated developing countries and areas.