The diagnosis of CFS/ME is entirely clinical: a characteristic pattern of somatic symptoms (see Centers for Disease Control and Prevention (CDC) case definition) dominated by unexplained fatigue limiting normal activity. Laboratory testing should be used to exclude other possible causes for the symptoms, but by far the most effective tool to use when CFS/ME is suspected is an activity scale or daily diary that measures a child's overall normal activity levels.

A child with CFS/ME will have substantially reduced activity levels, but may appear to others to have a normal activity level. For example, a child with CFS/ME may be able to participate in sporting activities on the weekend (i.e., playing in a soccer game), giving the appearance that she is healthy. On closer examination, however, the child with CFS/ME who participated in the soccer game would have to rest for the remainder of the day and usually the next day.

School attendance is the most important indicator of both severity and prognosis of pediatric CFS/ME. If the CFS/ME symptoms are mild, the child can make it through a full day of school, perhaps even with gym class, but will have increased fatigue and may need to rest often. Moderate CFS/ME permits part-time school without gym or sports and requires the child to get extra rest every evening.

With severe forms of CFS/ME, school attendance may not be possible, and home tutoring should be used to maintain an appropriate grade level.

Comparing the child's activity levels on weekends and during the summer to their activity during the school week is also important. Children often report that they feel better in the summer, which is often considered an indication of school phobia. However, it may actually be because fewer sustained activities are required.

Measuring activity levels helps to rule out school phobia or depression. Depressed children do not feel overly tired and weak. A child with CFS/ME will be just as inactive on the weekend as during the school week or may actually maintain less activity during unrestricted times.

Pediatric CFS is frequently misdiagnosed as a behavioral or emotional problem, in particular school phobia. Unlike children with school phobia, children with CFIDS are typically ill on weekends as well as during the school week. Many children with CFS also have orthostatic intolerance, which causes inability to tolerate upright posture.