In 2005, Panama experienced the largest dengue epidemic since 1993. We conducted both a prospective clinical and a national economic study. The full cost analysis measured costs of dengue cases and of dengue control efforts in the entire country. Costs are in 2005 US$. Ambulatory patients were 130 of the 136 participants, with 82% adults (18+) and 62% women. Duration of fever and illness averaged 6.1 (standard deviation [SD], 5.3) and 21.2 (SD 13.5) days, respectively. Loss in quality of life averaged 67% (SD 21) during the worst days of illness. An average ambulatory and hospitalized case cost $332 and $1,065, respectively. Although 5,489 cases were officially reported, the Ministry of Health (MOH) estimated 32,900 actual cases, implying a total cost of $11.8 million. Additionally, estimated government spending on dengue control efforts was $5 million. This dengue epidemic had a major disease impact and an economic cost of $16.9 million ($5.22 per capita).