Hantavirus Pulmonary Syndrome (HPS) is a viral infection carried by rodents and transmitted to humans. Increases in rodent population following El Niño precipitation in the Four Corners region of the United States and resulting increases in HPS cases have been studied; however, no such studies exist for the San Diego County region. Proportions of hantavirus positive rodents were compared for years with normal weather events and years where an El Niño event occurred between 1994 and 2009 in San Diego County. Annual precipitation was also evaluated to establish if weather effects played a significant role in proportion of hantavirus positive rodents as well. When comparing percent of rodents positive for hantavirus in the year following an El Niño event as compared to all other years sampled, rodents in the year following El Niño years were almost three times more likely to test positive for hantavirus that rodents during normal weather events (OR 2.96, 95% CI 1.98-4.41) El Niño years did not experience a statistically significant greater rainfall than normal weather years with the mean rainfall for normal year 8.1 inches (SD 5.0 inches) and the mean rainfall for El Niño years 12.1 inches (SD 6.4 inches) and a p-value of 0.35. The excess rains in a region like San Diego County likely allow for a great increase in plant growth and therefore rodent resources, allowing for an increase in the hantavirus vector. The increase in hantavirus positive rodents in any given region presents a public health concern as hantavirus has no vaccine or virus specific treatment and has a high case fatality rate. A better understanding of whether or not El Niño events correlate with increases in hantavirus positive rodents in San Diego County can allow for increased surveillance and public alerts to prevent human cases.