Sleepiness is a common perception during most infectious diseases, including viral infections. Previously, we observed that a lethal strain of influenza virus (H1N1) causes a greater increase in non-rapid eye movement sleep (NREMS) than a nonlethal strain of influenza virus (H3N2), suggesting that the magnitude of sleep responses after viral inoculation depends on the severity of the infection. The aim of the present experiment was to further test this possibility. The effects of total airway infection versus upper airway infection on sleep were tested in two groups of mice using the same strain of virus (H1N1). After 2-3 days of baseline sleep recordings. Swiss-Webster mice were infected intranasally with H1N1 influenza virus. Sleep was determined again for an additional 3 days and 6 hours. Total airway infection significantly increased NREMS beginning about 24 hours after the viral inoculation and significantly suppressed rapid eye movement sleep (REMS) with a longer latency. Both the increase in NREMS and the decrease in REMS lasted until the end of the experiment. Total airway infection also significantly decreased the body weight of the mice. In contrast, upper airway infection did not induce clear changes in sleep and body weight.