Abstract: Objective To investigate the relationship between serum levels of cobalt (Co) in children with hand foot and mouth disease (HFMD) and the severity of the symptoms manifested. Methods The children with HFMD were recruited in Shenzhen Children's Hospital from 2013 to 2015, and they were divided into severe group (202 cases)、mild group (220 cases), and control group(208 cases)according to their severity of symptom.For each child,a rectabl swab, a saliva swab, and a blood sample were collected. The types of pathogens infected was analyzed by real-time quantitative polymerase chain reaction(qPCR), and the levels of serum Co were detected by inductively coupled plasma mass spectrometry (ICP-MS). Results The average concentrations of serum Co in the severe, mild and control groups were 0.36 μg/kg, 0.40 μg/kg and 0.31 μg/kg, respectively. The serum Co levels in the severe group were significantly lower than other groups(all P<0.05), while there was no significant difference in levels of serum Co between the mild group and the control group (Z=-0.821,P=0.412). There were moderate negative correlation between the levels of Co and the severity of HFMD (r=-0.298,P<0.001). No significant differences of serum Co levels were observed among different genders and different age groups(all P>0.05), while significant differences were observed among different enterovirus tenterovirus types.The level of serum Coin children infected by EV71 were significantly higher than those infected by CA16 in the mild group(Z=4.397,P<0.001), while this difference was not observed in the severe group (Z=-1.821,P=0.069). And the results of Logistic regression analysis showed that with a certain range increase,of serum cobalt concentration, the risk of infected by HFMD decreased. Conclusions The level of cobalt (Co) in serum of children may have an effect on children's hand foot and mouth disease.